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S Frangou

Publications and source records attributed to S Frangou.

At least 19 recordsLinked to original sources
PubMed2006

The relationship of impulsivity to response inhibition and decision-making in remitted patients with bipolar disorder.

BACKGROUND: Impulsivity, a core feature of bipolar disorder (BD), is a multifaceted concept encompassing failure of response inhibition and poor decision-making. Abnormalities in these two cognitive domains have been reported in BD patients but their relationship with impulsivity has not been explored. METHODS: Twenty-five remitted patients with BD completed the Barratt Impulsiveness Scale (BIS) and performed the Hayling Sentence Completion Task (HSCT) and a computerized version of the Iowa Gambling task. The HSCT total errors scaled score was used as a measure of response inhibition while the gabling task score, which reflects participants' ability to make advantageous choices, was used a measure of decision making. RESULTS: Higher scores on the BIS attentional and non-planning subscales were respectively associated with more errors in the HSCT and less advantageous choices in the gambling task. LIMITATIONS: All patients were medicated. Healthy participants were not included. CONCLUSIONS: Viewed in the context of recent relevant studies our findings suggest that impulsivity, response inhibition and decision-making in BD may represent behavioural manifestations of the same underlying biological mechanism possibly linked to ventral prefrontal cortical function.

Attention↗
PubMed2006

Is there an association between the COMT gene and P300 endophenotypes?

P300 wave anomalies correlate with genetic risk for schizophrenia and constitute a plausible endophenotype for the disease. The COMT gene is thought to influence cognitive performance and to be a susceptibility gene for schizophrenia. Unlike two previous studies, we found no significant influence of the COMT gene on P300 amplitude or latency in 189 individuals examined. The well-supported role of the COMT gene both in dopamine catabolism as well as in prefrontal cognition makes a strong theoretical case for the influence of COMT Val158Met polymorphism on P300 endophenotypes. However, the available neurophysiologic evidence suggests that any such association, if present, must be very subtle.

Adult↗
PubMed2006

Fronto-temporal function may distinguish bipolar disorder from schizophrenia.

OBJECTIVES: There is evidence for differential neural alterations within the prefrontal cortex (PFC) in bipolar disorder I (BDI) and schizophrenia that may translate into different cognitive deficits. Our objective was to compare the cognitive profile of stable BDI and schizophrenic patients using neuropsychological tasks which utilize frontal systems but differ in terms of the exact neural circuits and cognitive processes involved. METHODS: We studied 43 patients with BDI, 54 with schizophrenia and 46 matched healthy participants. All participants completed (i) the Wisconsin Card Sorting Test (WCST) which is known to recruit the dorsal and ventral PFC, (ii) the verbal fluency task (VFT), which engages frontal-temporal regions, and (iii) the Stroop Colour Word Test (SWCT) which depends on the integrity of the cingulo-frontal network. A series of multivariate analyses examined differences between the cognitive profiles of BD and schizophrenic patients relative to that of healthy participants controlling for general intellectual ability and gender. RESULTS: Bipolar disorder I patients showed minimal verbal fluency impairment while schizophrenic patients demonstrated marked deficits on this task relative to the control and BDI groups. The two patient groups had comparable performance on the WCST. In the SWCT, schizophrenic patients showed impairment in both congruent and incongruent conditions while BD patients had deficits only in the latter. CONCLUSIONS: Absence of significant verbal fluency abnormalities and by inference dysfunction in the associated fronto-temporal circuitry may distinguish BDI from schizophrenia. Both disorders may show impairment in tasks involving cingulo-frontal networks with evidence of greater cingulate dysfunction in schizophrenia.

Adult↗
PubMed2005

The neurodevelopmental model of schizophrenia: update 2005.

Neurodevelopmental models of schizophrenia that identify longitudinal precursors of illness have been of great heuristic importance focusing most etiologic research over the past two decades. These models have varied considerably with respect to specificity and timing of hypothesized genetic and environmental 'hits', but have largely focused on insults to prenatal brain development. With heritability around 80%, nongenetic factors impairing development must also be part of the model, and any model must also account for the wide range of age of onset. In recent years, longitudinal brain imaging studies of both early and adult (to distinguish from late ie elderly) onset populations indicate that progressive brain changes are more dynamic than previously thought, with gray matter volume loss particularly striking in adolescence and appearing to be an exaggeration of the normal developmental pattern. This supports an extended time period of abnormal neurodevelopment in schizophrenia in addition to earlier 'lesions'. Many subtle cognitive, motor, and behavioral deviations are seen years before illness onset, and these are more prominent in early onset cases. Moreover, schizophrenia susceptibility genes and chromosomal abnormalities, particularly as examined for early onset populations (ie GAD1, 22q11DS), are associated with premorbid neurodevelopmental abnormalities. Several candidate genes for schizophrenia (eg dysbindin) are associated with lower cognitive abilities in both schizophrenic and other pediatric populations more generally. Postmortem human brain and developmental animal studies document multiple and diverse effects of developmental genes (including schizophrenia susceptibility genes), at sequential stages of brain development. These may underlie the broad array of premorbid cognitive and behavioral abnormalities seen in schizophrenia, and neurodevelopmental disorders more generally. Increased specificity for the most relevant environmental risk factors such as exposure to prenatal infection, and their interaction with susceptibility genes and/or action through phase-specific altered gene expression now both strengthen and modify the neurodevelopmental theory of schizophrenia.

Adult↗
PubMed2005

Telemonitoring of medication adherence in patients with schizophrenia.

Nonadherence to medication is a widespread problem in schizophrenia and is associated with poor clinical outcomes and inappropriate management and utilization of resources. The aim of the current investigation was to assess the impact of telemonitoring of medication adherence on symptomatology and service use in patients with schizophrenia. A total of 108 schizophrenia patients were randomized into three equal groups according to the approaches used to assess medication adherence; self-report, pill counting, and telemonitoring. Telementoring was achieved through an innovative new platform called @HOME. This platform offers clinicians early warnings about impeding nonadherence as well as information about the pattern of medication taking. Patient's adherence was observed over an 8-week period, during which patient's clinical status and service use were recorded. In comparison to the other two groups, patients using @HOME showed improvement in the Global Clinical Impression Scale and a significant reduction in emergency visits and medical appointments. The @HOME platform was highly acceptable by patients, caregivers, and professionals, and required minimal training for implementation. The results of the study suggest that the use of telemonitoring in psychiatric settings was both feasible and acceptable and may be associated with significant clinical and service related benefits.

Adult↗
PubMed2005

Aripiprazole in schizophrenia: consensus guidelines.

Schizophrenia is a chronic disabling disease which in the majority of cases requires long-term treatment with antipsychotic medication. Before the development of atypical antipsychotics, treatment choice was restricted to conventional (or typical) antipsychotics, which are known to cause a range of side effects including extrapyramidal symptoms. Although atypical agents provide a favourable alternative (advocated by the National Institute of Clinical Excellence in the UK), they are associated with side effects. These differ between agents, but can include weight gain, sedation and hyperprolactinaemia. Aripiprazole is a newly available atypical antipsychotic for the treatment of schizophrenia. With the apparent imitations of currently available medications, aripiprazole provides clinicians with another treatment option. The purpose of these guidelines is to outline the consensus reached by the Schizophrenia Innovation Working Group on best practice in prescribing and appropriate use of aripiprazole in the UK.

Antipsychotic Agents↗
PubMed2001

Structural magnetic imaging of the hippocampus in early onset schizophrenia.

BACKGROUND: Previous literature suggests that hippocampal volume reductions in schizophrenia may occur either during adolescence or at the point of transition to overt psychosis. The authors tested these hypotheses by examining the hippocampal formation in adolescents with recent onset schizophrenia. METHODS: We compared the volumes of the left and right hippocampus, obtained using stereologic methods from magnetic resonance brain images, from 40 adolescents with recent onset schizophrenia to those of an equal number of matched healthy control subjects. Symptoms were rated using the Positive and Negative Syndrome Scale. RESULTS: Compared with control subjects, adolescents with schizophrenia had reduced whole brain volume. After adjusting for brain volume, no group differences were observed in hippocampal volume. Duration of illness was negatively correlated with the volume of the left hippocampus. We found no effect of pregnancy and birth complications or family history of psychosis on hippocampal volumes. There was a negative correlation between severity of psychopathology and hippocampal volumes, which was significant for negative symptoms. CONCLUSIONS: Specific hippocampal volume reductions in early onset schizophrenia do not seem to predate the onset of or to occur at the point of transition to psychosis but may develop in adolescence during the early stages of the illness.

Adolescent↗
PubMed2001

Superior temporal gyrus abnormalities in early-onset schizophrenia: similarities and differences with adult-onset schizophrenia.

OBJECTIVE: The superior temporal gyrus is associated with developmental mechanisms of brain lateralization and the pathogenesis of language-related schizophrenic symptoms. It therefore lends itself to investigation of developmental deviance in the early onset of schizophrenia. METHOD: Using stereological methods, the authors obtained bilateral measurements of the superior temporal gyrus (total, gray matter, and white matter volumes) from 40 adolescents with recent-onset schizophrenia and an equal number of matched healthy volunteers. Symptoms were rated by using the Positive and Negative Syndrome Scale. RESULTS: The total and gray matter volume of the right superior temporal gyrus was significantly lower in patients with early-onset schizophrenia than in the healthy volunteers, even after differences in whole brain volume were controlled. Bilateral superior temporal gyrus volumes were positively correlated with the age at onset of psychosis, while severity of thought disorder and hallucinations were inversely related to right superior temporal gyrus volume. CONCLUSIONS: In patients with early-onset schizophrenia, the predominantly right-sided volumetric abnormalities found in the superior temporal gyrus may reflect a particularly early neurodevelopmental disruption. The relationship between language-related symptoms and superior temporal gyrus volume is similar to that seen in adult-onset cases but not as lateralized.

Adolescent↗
PubMed2001

Service use and costs of treating schizophrenia with atypical antipsychotics.

BACKGROUND: The high acquisition cost of the atypical antipsychotics has prompted their closer clinical and economic evaluation. This study aims to examine the financial implications of using atypical antipsychotics in a defined catchment area sample of patients with schizophrenia. METHOD: Service costs over a 10-month period were compared between groups of patients fulfilling DSM-IV criteria for schizophrenia who were taking different atypical antipsychotic agents. RESULTS: All patients studied were taking clozapine (N = 31). risperidone (N = 19), or olanzapine (N = 41). Clozapine was used in more chronic patients, while risperidone and olanzapine were prescribed in both chronic and recently diagnosed cases. After background group differences were controlled for, patients on risperidone treatment incurred the lowest costs. The monthly costs for the clozapine and olanzapine groups were higher than for risperidone by US $246 and US $566, respectively. CONCLUSION: Clozapine was reserved for more severe forms of schizophrenia, but its cost impact was relatively low. Risperidone, as prescribed in ordinary practice, may be more cost-effective than olanzapine.

Adult↗
PubMed2000

Atypical antipsychotics in ordinary clinical practice: a pharmaco-epidemiologic survey in a south London service.

The introduction of atypical antipsychotics has triggered a reevaluation of treatment strategies in schizophrenia. Although research findings inform about the efficacy and safety of drugs, it is the decisions made daily in ordinary practice that affect the vast majority of patients. The aim of this paper was to examine the use of atypical antipsychotics in clinical care, by means of a survey of prescribing practices for clozapine, risperidone, olanzapine, sertindole and quetiapine for all patients treated for DSM-IV schizophrenia within a psychiatric service. Seventy-five (26%) of the 286 patients identified were on atypical antipsychotics. Patients on clozapine were mostly male, had more than 15 years of contact with psychiatric services and were poor responders. Patients prescribed other atypicals had responded to prior treatment with typical neuroleptics and had less than five years of contact with psychiatric services. Gender distribution was equal in this group. The use of research criteria for treatment resistance identified only one patient, as prolonged use of high-dose neuroleptics was uncommon. The new atypical antipsychotics appear to be replacing older neuroleptics as the first-line treatment of schizophrenia while clozapine is mostly reserved for poor responders. Clinicians' definition of treatment resistance was variable and below the threshold used in research.

Adult↗
PubMed1999

Hippocampal volume reduction in schizophrenia: effects of genetic risk and pregnancy and birth complications.

BACKGROUND: Hippocampal volume reduction has been repeatedly demonstrated in schizophrenia. The relative contribution of genetic and environmental factors to this is unclear. METHODS: To address this question, we compared volumetric measurements of the left and right hippocampus, obtained using stereological methods from brain MRI scans, from two groups of patients with schizophrenia as well as healthy controls (n = 26). Patients (n = 27) in the first group, had no family history of schizophrenia and had experienced severe pregnancy and birth complications (PBCs). The second group comprised of patients (n = 21) without a history of severe PBCs from families multiply affected with schizophrenia. RESULTS: Reduction of the left hippocampal volume was associated with the diagnosis of schizophrenia but was present only in patients with a history of severe PBCs; in this group the smaller hippocampal volume, the earlier the onset of psychosis. CONCLUSIONS: Our findings suggest that environmental factors, in this case severe PBCs, make a significant contribution to hippocampal abnormalities in schizophrenia.

Adult↗
PubMed1998

Minor physical anomalies in familial and sporadic schizophrenia: the Maudsley family study.

OBJECTIVES: (1) To test the hypothesis that minor physical anomalies are increased in patients with schizophrenia and (2) to investigate differences in the prevalence of minor physical anomalies in patients with familial and sporadic schizophrenia and their first degree relatives. METHODS: A weighted Waldrop assessment was carried out on 214 subjects in five groups: schizophrenic patients from multiply affected families; first degree relatives of these familial schizophrenic patients; sporadic schizophrenic patients; first degree relatives of these sporadic schizophrenic patients, and normal controls. Broad and narrow criteria for abnormality were defined based on the distribution of minor physical anomalies in the control group. RESULTS: (1) The total schizophrenic group did not have a significant increase in minor physical anomalies using a narrow criterion of abnormality, but did when a broader criterion was used. (2) A significant increase in the proportion of subjects with an abnormally high number of minor physical abnormalities was shown in the group of sporadic schizophrenic patients (uncorrected p<0.01). Separate analyses for males and females showed a significant increase in the male sporadic group (uncorrected p<0.05), and a smaller non-significant increase in the female sporadic group. Neither the familial schizophrenic group nor either group of first degree relatives showed any significant increases in the proportion of patients with high abnormality scores. CONCLUSION: This work supports prenatal developmental abnormality as a mechanism for sporadic, but not familial, schizophrenia.

Adult↗
PubMed1998

MRI brain changes in subjects with Down syndrome with and without dementia.

Individuals with Down syndrome (DS), a disorder of known genetic etiology (trisomy of chromosome 21), exhibit several types of structural brain abnormalities that are detectable pathologically and by MRI. In addition, in middle age, individuals with DS develop histological and, in some cases, clinical features of Alzheimer's disease (AD). Abnormalities in MRI scans of 50 adults with DS, 11 of whom had clinical dementia, are described and compared with those of 23 cognitively normal, healthy subjects who were matched for age, sex, and race. Qualitative visual analogue scale (VAS) ratings on MRI hard copies for all subjects and computer-aided volume measures for a subsample of subjects were carried out. On VAS, subjects with DS had larger lateral ventricles, a higher frequency of posterior fossa arachnoid cysts/megacisterna magna and fewer scans rated as normal compared with controls. Quantitatively, total brain and gray-matter volumes were reduced in DS, as were the volumes of the left hippocampus and amygdala; ventricle volumes were larger. Post hoc comparisons of subjects with DS with and without dementia revealed that on VAS the former had more generalized atrophy for age, mesial temporal shrinkage, and third ventricular enlargement. Similarly, total brain, left hippocampus, and left amygdala volumes were reduced quantitatively in subjects with DS with dementia, while ventricular volumes were increased.

Adult↗
PubMed1997

The dysplastic net hypothesis: an integration of developmental and dysconnectivity theories of schizophrenia.

Two separate theories that attempt to explain different aspects of schizophrenia have recently attracted much attention. The first, the neurodevelopmental hypothesis, postulates that deviations in early development establish a neuronal phenotype that predisposes to, or, in some versions, determines the later onset of schizophrenia. The second theory proposes that schizophrenic symptoms arise from abnormalities in neuronal connectivity. Here, we suggest that the findings from these two separate lines of inquiry can be integrated into a unitary framework: the dysplastic net hypothesis. In essence, this proposes that anatomical and physiological dysconnectivity of the adult schizophrenic brain is determined by dysplastic fetal brain development. We also indicate how abnormal connectivity between brain regions constituting large-scale neurocognitive networks is expressed in both the prepsychotic and psychotic phases of schizophrenia, and we examine possible risk factors (genetic and environmental) for dysplastic formation of these networks.

Adult↗
PubMed1997

The Maudsley Family Study, II: Endogenous event-related potentials in familial schizophrenia.

Auditory event-related potentials (ERPs) were obtained from 33 schizophrenics, from 16 families multiply affected with schizophrenia, 57 of their non-schizophrenic first-degree relatives and 32 unrelated healthy controls. Transmission of schizophrenia in these families appeared unilinear with one parent only transmitting the disorder. Consequently, we were able to identify 10 presumed obligate carriers and study eight of them. Schizophrenic patients showed latency prolongation and amplitude reduction of the N100, N200 and P300 waves compared to controls. Their relatives showed similar abnormalities compared to controls. There was a trend for bimodal distribution of the P300 latency in the relatives, with 20 (35%) of them falling outside two standard deviations of the mean of the controls. These included six of the eight obligate carriers. Our results suggest that ERP abnormalities may serve as markers of genetic vulnerability in schizophrenia and may be useful in genetic linkage studies.

Adult↗
PubMed1997

Small planum temporale volume in Down's syndrome: a volumetric MRI study.

OBJECTIVE: Down's syndrome is associated with structural brain abnormalities and language deficits. The aim of this study was to investigate whether the superior temporal gyrus and the planum temporale, both parts of the anatomic substrate for language, are abnormal in Down's syndrome. METHOD: The authors examined volumetric magnetic resonance imaging (MRI) measures of the superior temporal gyrus and the planum temporale for 17 community-dwelling patients with Down's syndrome and 17 matched healthy comparison subjects. For the subjects with Down's syndrome, the correlations of the superior temporal gyrus and planum temporale volumes with performance on tests of language function were examined. RESULTS: The planum temporale volume of the patients with Down's syndrome was smaller than that of the healthy subjects, even after differences in whole brain volume were controlled for. The volume of the superior temporal gyrus in the Down's syndrome patients was proportionally similar to that of the comparison group. For the subjects with Down's syndrome, neither superior temporal gyrus nor planum temporale volume was significantly correlated with performance on language tests after total brain volume was controlled for. CONCLUSIONS: In Down's syndrome, planum temporale volume may be selectively smaller than normal, although the effect of this volume deficit on language is not clear.

Adult↗
PubMed1997

Planum temporale asymmetry reversal in schizophrenia: replication and relationship to gray matter abnormalities.

OBJECTIVE: The planum temporale, the posterior superior surface of the superior temporal gyrus, is a highly lateralized brain structure involved with language. In schizophrenic patients the authors previously found consistent reversal of the normal left-larger-than-right asymmetry of planum temporale surface area. The original subjects plus new patients and comparison subjects participated in this effort to replicate and extend the prior study. METHOD: High-resolution magnetic resonance imaging of 28 schizophrenic patients and 32 group-matched normal subjects was performed. The authors measured planum temporale surface area, gray matter volume underlying the planum temporale, and gray matter thickness. Asymmetry indices for areas and volumes were calculated. RESULTS: Overall gray matter and total brain volume were not significantly smaller in the patients than in the comparison subjects. As previously reported, there was striking reversal of the normal asymmetry for planum temporale surface area in the male and female schizophrenic subjects. Bilaterally, gray matter volume beneath the planum temporale was smaller in the schizophrenic patients, and the gray matter thickness of the right planum temporale was only 50% of the comparison value. Volume of planum temporale gray matter did not show significant asymmetry in either group. CONCLUSIONS: This study extends the finding of reversed planum temporale surface area asymmetry in schizophrenic patients and clarifies its relationship to underlying gray matter volume. Although right planum temporale surface area is larger than normal in schizophrenia, gray matter volume is less than the comparison value; thus, gray matter thickness is substantially less than normal.

Adult↗