Biomedical subjects

Sophia Frangou

Publications and source records attributed to Sophia Frangou.

At least 19 recordsLinked to original sources

PubMed2006

Preliminary in vivo evidence of increased N-acetyl-aspartate following eicosapentanoic acid treatment in patients with bipolar disorder.

Ethyl-eicosapentanoic acid (ethyl-EPA) may be beneficial in the treatment of bipolar disorder (BD) and may have a neurotrophic/neuroprotective role in patients with neuropsychiatric disorders. To investigate this we examined whether ethyl-EPA treatment of BD patients is associated with increased brain levels of N-acetylaspartate (NAA), a putative marker of neuronal integrity. Fourteen female BD outpatients with moderate depressive symptoms were administered 2 g of ethyl-EPA per day or placebo for 12 weeks in a randomized, double-blind fashion. Quantitative, proton magnetic resonance spectroscopy imaging data were obtained prior to randomization and after 12 weeks of treatment from a single 12 ml volume of interest centred above the body of the corpus callosum. A significant rise in NAA levels was observed in the ethyl-EPA treatment group compared with the placebo group (p = 0.027). These results provide the first evidence for a probable neurotrophic role of ethyl-EPA treatment in BD underlining the need for more detailed investigation of its mechanism of action and therapeutic potential.

Adult↗

PubMed2006

Increased prepulse inhibition of the acoustic startle response is associated with better strategy formation and execution times in healthy males.

Prepulse inhibition (PPI) refers to the attenuation of the amplitude of the startle reflex in response to sudden intense stimuli (pulse) if preceded by a weaker sensory stimulus (prepulse). PPI reflects the ability to filter out irrelevant information in the early stages of processing so that attention can be directed to more salient environmental features. Inhibition at this early stage of information processing appears modulated by the prefrontal cortex in a "top-down" fashion and this may account for the normal inter-individual variability in PPI and in cognitive performance. PPI data were calculated from 82 healthy male subjects who were also tested in problem solving (Stockings of Cambridge; SoC), spatial working memory (SWM) and 5-choice reaction time (RT) tests from the Cambridge Neuropsychological Test Automated Battery. Correlations between PPI scores and cognitive test variables were examined. In addition PPI scores were divided in quartiles which were used as grouping factors in examining cognitive test performance. Compared to individuals in the lowest quartile those in the highest had (a) shorter execution but not reaction times on the 5-choice RT, (b) shorter subsequent but not initial thinking times in the SoC where they also solved more problems correctly with the minimum number of moves, and (c) better strategy but not errors scores in the SWM. Our findings suggest that greater PPI is associated with superior abilities in strategy formation and execution times. We suggest that this is due to more efficient early information processing.

Acoustic Stimulation↗

PubMed2006

The level of prepulse inhibition in healthy individuals may index cortical modulation of early information processing.

This study examined whether baseline PPI levels reflect individual efficiency in tasks associated with routine versus supervisory attentional systems (SAS). PPI and neuropsychological data were collected from 30 healthy male subjects. High PPI was associated with shorter movement times on the 5-choice Reaction Time and shorter Subsequent Thinking Times in the Stockings of Cambridge test. These data suggest that high-PPI status reflects greater efficiency in tasks that engage SAS.

Acoustic Stimulation↗

PubMed2006

Stroop performance in bipolar disorder: further evidence for abnormalities in the ventral prefrontal cortex.

OBJECTIVES: Bipolar patients are impaired in Stroop task performance, a measure of selective attention. Structural and functional abnormalities in task-associated regions, in particular the prefrontal cortex (PFC), have been reported in this population. We aimed to examine the relationship between functional abnormalities, impaired task performance and the severity of depressive symptoms in bipolar patients. METHODS: Remitted bipolar patients (n = 10; all medicated), either euthymic or with subsyndromal depression, and age-matched control subjects (n = 11) viewed 10 alternating blocks of incongruent Stroop and control stimuli, naming the colour of the ink. Neural response was measured using functional magnetic resonance imaging. We computed between-group differences in neural response and within-group correlations with mood and anxiety. RESULTS: There were no significant between-group differences in task performance. During the Stroop condition, controls demonstrated greater activation of visual and dorsolateral and ventrolateral prefrontal cortical areas; bipolar patients demonstrated relative deactivation within orbital and medial prefrontal cortices. Depression scores showed a trend towards a negative correlation with the magnitude of orbitofrontal cortex deactivation in bipolar patients, whereas state anxiety correlated positively with activation of dorsolateral PFC and precuneus in controls. CONCLUSIONS: Our findings confirm previous reports of decreased ventral prefrontal activity during Stroop task performance in bipolar patients, and suggest a possible negative correlation between this and depression severity in bipolar patients. These findings further highlight the ventromedial PFC as a potential candidate for illness related dysfunction in bipolar disorder.

Adult↗

PubMed2006

Efficacy of ethyl-eicosapentaenoic acid in bipolar depression: randomised double-blind placebo-controlled study.

BACKGROUND: Epidemiological and clinical studies suggest that increased intake of eicosapentaenoic acid (EPA) alleviates unipolar depression. AIMS: To examine the efficacy of EPA in treating depression in bipolar disorder. METHOD: In a12-week, double-blind study individuals with bipolar depression were randomly assigned to adjunctive treatment with placebo (n=26) or with 1 g/day (n=24) or 2 g/day (n=25) of ethyl-EPA. Primary efficacy was assessed by the Hamilton Rating Scale for Depression (HRSD), with changes in the Young Mania Rating Scale and Clinical Global Impression Scale (CGI) as secondary outcome measures. RESULTS: There was no apparent benefit of 2 g over 1 g ethyl-EPA daily. Significant improvement was noted with ethyl-EPA treatment compared with placebo in the HRSD (P=0.04) and the CGI (P=0.004) scores. Both doses were well tolerated. CONCLUSIONS: Adjunctive ethyl-EPA is an effective and well-tolerated intervention in bipolar depression.

Adult↗

PubMed2005

Is the P300 wave an endophenotype for schizophrenia? A meta-analysis and a family study.

INTRODUCTION: We assessed the usefulness of the P300 wave as endophenotype for schizophrenia by means of a meta-analysis of the literature as well as our own family study. METHOD: Meta-analysis: We conducted a systematic search for articles published between 1983 and 2003 that reported P300 measures in non-psychotic relatives of schizophrenic patients and in healthy controls. Meta-regression analyses were performed using a random effects procedure. The pooled standardized effect size (PSES) was calculated as the difference between the means of the two groups divided by the common standard deviation. Local study: We examined the P300 wave with a standard two-tone oddball paradigm in 30 patients with schizophrenia, 40 non-psychotic relatives, and 40 controls using linear mixed models. RESULTS: Meta-analysis: We pooled 472 relatives and 513 controls. The P300 amplitude was significantly reduced in relatives (PSES = 0.61; 95% CI: 0.30 to 0.91; P < 0.001). The P300 latency was significantly delayed in relatives (PSES of -0.50; 95% CI: -0.88 to -0.13; P = 0.009]. Local study: The patients showed a trend for amplitude reductions (P = 0.06) and significant latency delays (P < 0.01). The relatives displayed normal amplitude but had significant latency delays (P = 0.01). The P300 amplitude and especially the P300 latency are promising alternative phenotypes for genetic research into schizophrenia.

Adolescent↗

PubMed2005

The effects of dopamine agonists on prepulse inhibition in healthy men depend on baseline PPI values.

RATIONALE AND OBJECTIVES: Dopamine (DA) agonists reliably disrupt prepulse inhibition (PPI) of the startle reflex in animals but less so in humans despite cross-species similarities in the neural regulation of PPI. This study examines whether individual variation in baseline PPI may account for the inconsistencies in DA agonist-induced PPI disruption in humans. METHODS: Baseline PPI measures were obtained from 32 healthy adult men. Subjects were subsequently tested in three sessions after ingestion of placebo or active drug in a balanced double-blind design. Seventeen subjects were given 0.05 and 0.1 mg of pergolide (a direct DA agonist) and 15 subjects were given 100 and 200 mg of amantadine (an indirect DA agonist). In each treatment group, subjects were assigned to "high" and "low" PPI subgroups based on the median split of their baseline PPI. RESULTS: Amantadine and pergolide disrupted PPI in high- but not in low-PPI subjects. In contrast, low-PPI subjects showed a trend towards PPI facilitation especially with pergolide. CONCLUSIONS: Our results suggest that baseline PPI is an important determinant of the effect of DA agonists on PPI.

Acoustic Stimulation↗

PubMed2005

Validation of the Investigator's Assessment Questionnaire, a new clinical tool for relative assessment of response to antipsychotics in patients with schizophrenia and schizoaffective disorder.

The success of long-term therapy in schizophrenia is contingent upon real-world effectiveness or improvements in several domains, including efficacy, safety and tolerability. This report describes the Investigator's Assessment Questionnaire (IAQ), a new 10-item instrument designed to assess relative effectiveness (efficacy, safety and tolerability) of antipsychotic medications in patients with schizophrenia or schizoaffective disorder. To measure content validity, 300 psychiatrists rated the importance of the IAQ items. Efficacy (i.e., positive and negative symptoms) was considered most important, but importance scores relative to the mean ranged only from 0.87 to 1.18, suggesting similar importance of the items. Cronbach's coefficient alpha values showed that the items were internally consistent. Factor analyses indicated that all IAQ items belong to a single domain. Data from the US Broad Effectiveness Trial of Aripiprazole were used for construct validation. Total IAQ score correlated significantly with time to treatment discontinuation (r=-0.50), Clinical Global Impressions-Improvement (CGI-I) score (r=0.76) and medication preference of patients (r=0.71) or caregivers (r=0.70). A one-unit decrease in IAQ score corresponded to an additional 1.35 days in the study and a decrease in CGI-I of 0.21 units. These results provide initial validation of the IAQ as a tool for evaluating antipsychotic response in patients with schizophrenia or schizoaffective disorder.

Adolescent↗

PubMed2005

Evidence for deficit in tasks of ventral, but not dorsal, prefrontal executive function as an endophenotypic marker for bipolar disorder.

BACKGROUND: Trait functional abnormalities in BD patients have only been reported in the ventral prefrontal cortex (VPFC). We examined whether deficits in VPFC-related inhibitory processes, but not dorsal prefrontal (DPFC) based executive functions, represent an endophenotypic marker for bipolar disorder I (BDI). METHODS: We used the Wisconsin Card Sorting Test (WCST), commonly associated with DPFC function, and the Hayling Sentence Completion Task (HSCT) which engages the VPFC. Performance on these tests of 43 healthy participants was compared to that of 10 remitted BDI patients and 15 of their unaffected offspring. RESULTS: Compared to healthy participants, patients and their offspring made more errors in the HSCT but offspring achieved more categories and made fewer perseverative errors in the WCST. CONCLUSIONS: Impaired response inhibition, predominantly a VPFC related function, may reflect familial predisposition to BDI while deficits in rule attainment, a DPFC based function, may be associated only with the clinical phenotype.

Adult↗

PubMed2005

The Maudsley Bipolar Disorder Project: executive dysfunction in bipolar disorder I and its clinical correlates.

BACKGROUND: Cognitive abnormalities are increasingly recognized as a feature of bipolar I disorder (BDI,) but there is limited information regarding the pattern and severity of cognitive impairment during remission and its relationship with clinical variables. METHODS: Forty-four remitted BDI patients recruited from a representative treatment sample and an equal number of matched healthy volunteers underwent comprehensive clinical and cognitive assessments. Cognitive evaluation covered the domains of IQ, memory, and executive function. The profile of cognitive deficits in patients was examined, and the correlation of executive function with clinical features and treatment variables was explored. RESULTS: Remitted BDI patients were impaired in tests of executive function compared with healthy participants. Within the patient group, current antipsychotic treatment predicted worse performance across all executive function tests, whereas duration of illness predicted loss of inhibitory control. Residual mood symptoms, regardless of polarity, had a negative impact primarily on measures of attentional interference. CONCLUSIONS: These results suggest that impaired executive function might be an important feature of BDI. Antipsychotic treatment, duration of illness, and level of symptoms are the most significant contributors to the observed impairment.

Adolescent↗

PubMed2005

Hyperactivity in adolescents born very preterm is associated with decreased caudate volume.

BACKGROUND: Several studies have associated preterm birth with impaired behavioral functioning and attention problems. In addition, preterm individuals have an increased risk of brain injury in the neonatal period. Such early lesions have the potential to disrupt subsequent neurodevelopment. This study explored behavioral functioning, particularly externalizing behavior, in a group of adolescents who were born very preterm and its relationship with volume of the caudate, a brain region particularly vulnerable to damage in the preterm neonate. METHODS: We studied 72 adolescents born before 33 weeks and 50 age- and gender-matched full-term control subjects. Behavioral assessment included the Rutter Behavioural Scale and a social adjustment scale. Bilateral caudate volumes were quantified by stereologic methods. RESULTS: Preterm adolescents scored significantly higher than control subjects on the Rutter hyperactivity score, and boys scored higher than girls. In preterm boys only, left caudate volume was negatively correlated with hyperactivity score (r = -.43, p = .018) and social adjustment score in childhood (r = -.40, p = .028). CONCLUSIONS: Our data suggest that boys born very preterm are more likely to experience nonclinical behavioral problems in adolescence compared with full-term control subjects. Our results indicate that behavioral problems in this group might be associated with reductions in volume of the left caudate nucleus.

Adolescent↗

PubMed2005

Is the prophylactic antidepressant efficacy of lithium in bipolar I disorder dependent on study design and lithium level?

In the 1970s, several randomized controlled trials demonstrated significant antimanic and antidepressant properties of lithium in the prophylactic treatment of bipolar disorder. However, a recent meta-analysis of randomized, placebo-controlled trials of lithium in bipolar disorder found that its protective effect against depressive relapse/recurrence was equivocal. By examining potentially relevant parameters of recent randomized controlled trials with regard to lithium's prophylactic antidepressant efficacy, we try to identify factors which might help to explain these discrepant results across the different trials. Lithium's efficacy against manic relapse/recurrence appears rather robust at plasma levels between 0.8 and 1.2 mmol/L, whereas lithium's efficacy against depressive relapse/recurrence may be more modest and dependent on whether a response during the preceding acute episode was achieved by lithium treatment. Furthermore, it might be advisable to continue lithium without interruption at the same dose/plasma level, which yielded the initial response. A lithium level between 0.5 and 0.8 mmol/L may be equally efficacious against overall relapse and associated with equal or even superior efficacy regarding depressive relapse/recurrence. To provide evidence-based guidelines on this issue, large prospective, randomized, double-blind, placebo-controlled trials are needed comparing the efficacy of lithium at different plasma levels against manic and depressive relapse/recurrence. In these trials, factors previously associated with predicting response to lithium should also be assessed.

Antidepressive Agents↗

PubMed2005

The Maudsley Bipolar Disorder Project.

PURPOSE: The Maudsley Bipolar Disorder Project set out to investigate the cognitive and brain structural and functional characteristics of Bipolar Disorder I (BDI). METHODS: Participating patients were recruited while in remission from a secondary care setting and were matched to healthy volunteers in terms of age, gender, race, and years of education. All participants underwent extensive clinical and cognitive assessment. Brain structural and functional data also were obtained by using magnetic resonance imaging (MRI). RESULTS: Compared with controls, patients showed subtle widespread decrements, with executive function being more markedly impaired. Patients also showed volume decrements in the ventral prefrontal cortex (VPFC) bilaterally and the dorsal PFC (DPFC) on the left, whereas the volume of the amygdala was bilaterally enlarged. Patients showed subtle abnormalities in functional MRI in their DPFC, with marked decrements in activity in both the DPFC and VPFC in tasks that rely on the functional interaction of these brain regions. CONCLUSIONS: Our results suggest that BDI is associated with trait deficits in executive function and in the structure and function of the PFC.

Adult↗

PubMed2004

Meta-analysis of the P300 and P50 waveforms in schizophrenia.

OBJECTIVE: To determine whether patients with schizophrenia have abnormalities in the P300 and P50 waves and to quantify the magnitude of any differences from controls. METHOD: We conducted a systematic search for articles published between January 1994 and August 2003 that reported P50 or P300 measures in schizophrenic patients and controls. Metaregression analyses were performed using a random effects model. The pooled standardised effect size (PSES) was calculated as the difference between the means of the two groups divided by the common standard deviation. RESULTS: We identified 46 studies suitable for analysis of P300 measures, including 1443 patients and 1251 controls. There were 20 P50 studies including 421 patients and 401 controls. The PSES for the P300 amplitude was 0.85 (95% CI: 0.65 to 1.05; p<0.001), and for the P300 latency was -0.57 (95% CI: -0.75 to -0.38; p<0.001). The PSES of the P50 ratio was -1.56 (95% CI: -2.05 to -1.06; p<0.001). There were no significant differences between patients and controls in P50 latency. Across-study variations in filters, task difficulty, antipsychotic medication and duration of illness did not influence the PSES significantly. CONCLUSIONS: This meta-analysis confirms the existence of ERP deficits in schizophrenia. The magnitude of these deficits is similar to the most robust findings reported in neuroimaging and neuropsychology in schizophrenia.

Antipsychotic Agents↗

PubMed2004

Subcortical and ventral prefrontal cortical neural responses to facial expressions distinguish patients with bipolar disorder and major depression.

BACKGROUND: Bipolar disorder (BD) is characterised by abnormalities in mood and emotional processing, but the neural correlates of these, their relationship to depressive symptoms, and the similarities with deficits in major depressive disorder (MDD) remain unclear. We compared responses within subcortical and prefrontal cortical regions to emotionally salient material in patients with BP and MDD using functional magnetic resonance imaging. METHODS: We measured neural responses to mild and intense expressions of fear, happiness, and sadness in euthymic and depressed BD patients, healthy control subjects, and depressed MDD patients. RESULTS: Bipolar disorder patients demonstrated increased subcortical (ventral striatal, thalamic, hippocampal) and ventral prefrontal cortical responses particularly to mild and intense fear, mild happy, and mild sad expressions. Healthy control subjects demonstrated increased subcortical responses to intense happy and mild fear, and increased dorsal prefrontal cortical responses to intense sad expressions. Overall, MDD patients showed diminished neural responses to all emotional expressions except mild sadness. Depression severity correlated positively with hippocampal response to mild sadness in both patient groups. CONCLUSIONS: Compared with healthy controls and MDD patients, BD patients demonstrated increased subcortical and ventral prefrontal cortical responses to both positive and negative emotional expressions.

Adult↗

PubMed2004

Mismatch negativity in schizophrenia: a family study.

BACKGROUND: Mismatch negativity (MMN) is a measure of cortical activity that occurs in response to a change in auditory stimuli. We investigated whether MMN is a potential marker of genetic vulnerability to schizophrenia by comparing MMN in a group of patients with schizophrenia, their unaffected relatives, and controls. METHOD: There are 25 schizophrenic patients, 37 of their unaffected first-degree relatives, and 20 unrelated controls that performed the MMN task. Linear regression with robust standard errors, and accounting for correlations within families, was employed to test for differences in MMN amplitude between the groups. RESULTS: Patients had significantly smaller MMN amplitudes compared to both their unaffected relatives and controls at FZ (P<0.01) and at F3 (P=0.01), whereas relatives and controls did not differ at FZ or at F3. No differences were found between any of the groups at F4. Furthermore, we found no strong evidence that the MMN amplitude is a familial trait. CONCLUSIONS: Our results confirm that the MMN amplitude is reduced in schizophrenia. However, the MMN does not show a significant familial influence and is normal among the unaffected relatives. We conclude that while the MMN is abnormal in patients with schizophrenia, it is a weak or unreliable marker of vulnerability when applied to subclinical populations, and therefore is unlikely to be an endophenotype for the disorder.

Acoustic Stimulation↗

PubMed2004

Normal cerebral volume asymmetries in early onset schizophrenia.

BACKGROUND: Abnormalities in cerebral lateralization are thought to reflect early neurodevelopmental defects in schizophrenia. The aim of this study was to examine whether there is abnormal brain lateralization in early onset schizophrenia (EOS) and whether it is related to the unusually early onset of the disorder. METHODS: Adolescent patients with recent onset schizophrenia and an equal number of matched control subjects participated in the study. The volumes of the occipitoparietal, sensorimotor, premotor, prefrontal, and temporal regions were measured bilaterally from magnetic resonance images using stereological methods. Asymmetry indexes were calculated for each region using the formula ([R - L]/[R + L]) x 100. A composite index of asymmetry (torque) was computed as the sum of the five index scores. RESULTS: A total of 40 patients with EOS and 40 age-matched controls were enrolled. There were no group differences in demographic characteristics. No group differences in brain asymmetry measures were seen in any of the brain regions examined. CONCLUSIONS: The unusually early onset of schizophrenia in this population does not appear to be associated with abnormalities in hemispheric lateralization.

Adolescent↗

PubMed2004

Mapping IQ and gray matter density in healthy young people.

Magnetic resonance imaging (MRI) studies suggest that significant changes in gray matter density occur during adolescence because of brain maturation. It has also been reported that gray matter volume correlates with measures of intellectual ability. This study examined whether the relationship between general intellectual ability (IQ) and gray matter morphometry reflects differential involvement of particular cytoarchitectonic areas. We found positive correlations between IQ and gray matter density in the orbitofrontal cortex, cingulate gyrus, the cerebellum, and thalamus and negative correlations in the caudate nucleus. These findings suggest that general intellectual ability in healthy young people is related to specific brain regions known to be involved in the executive control of attention, working memory, and response selection.

Adolescent↗