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Stefano Marenco

Publications and source records attributed to Stefano Marenco.

11 recordsLinked to original sources
PubMed2006

Regional distribution of measurement error in diffusion tensor imaging.

The characterization of measurement error is critical in assessing the significance of diffusion tensor imaging (DTI) findings in longitudinal and cohort studies of psychiatric disorders. We studied 20 healthy volunteers, each one scanned twice (average interval between scans of 51 +/- 46.8 days) with a single shot echo planar DTI technique. Intersession variability for fractional anisotropy (FA) and Trace (D) was represented as absolute variation (standard deviation within subjects: SDw), percent coefficient of variation (CV) and intra-class correlation coefficient (ICC). The values from the two sessions were compared for statistical significance with repeated measures analysis of variance or a non-parametric equivalent of a paired t-test. The results showed good reproducibility for both FA and Trace (CVs below 10% and ICCs at or above 0.70 in most regions of interest) and evidence of systematic global changes in Trace between scans. The regional distribution of reproducibility described here has implications for the interpretation of regional findings and for rigorous pre-processing. The regional distribution of reproducibility measures was different for SDw, CV and ICC. Each one of these measures reveals complementary information that needs to be taken into consideration when performing statistical operations on groups of DT images.

Adult↗
PubMed2006

Anti-N-methyl-D-aspartate receptor antibodies, cognitive dysfunction, and depression in systemic lupus erythematosus.

OBJECTIVE: To assess the association of cognitive dysfunction and depression with serum antibodies to N-methyl-D-aspartate (NMDA) receptor (anti-NR2) and analyze clinical and neuroimaging correlates in patients with systemic lupus erythematosus (SLE). METHODS: Sixty patients underwent neurocognitive assessment, evaluation for depression with the Beck Depression Inventory II (BDI-II) and psychiatric interview (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition [DSM-IV] criteria), brain magnetic resonance imaging, and proton magnetic resonance spectroscopy imaging (1H-MRSI). Cognition was assessed in 5 domains: memory, attention/executive, visuospatial, motor, and psychomotor, and adjusted to each individual's best level of prior cognitive functioning estimated from the reading subtest of the Wide Range Achievement Test-3 (WRAT-3). Serum anti-NR2 antibodies were measured by enzyme-linked immunosorbent assay using a pentapeptide from the human NMDA receptor. RESULTS: Cognitive dysfunction was found in 28 of 60 patients (mild in 8, moderate in 20) before adjustment for WRAT-3 and in 35 of 60 patients (mild in 15, moderate in 11, and severe in 9) after adjustment for WRAT-3. The changes were most pronounced in the memory and visuospatial domains. There was no significant association between anti-NR2 antibody levels and cognition. On 1H-MRSI, patients with moderate or severe cognitive dysfunction had significantly higher choline:creatine ratios in the dorsolateral prefrontal cortex and the white matter, compared with patients with mild or absent cognitive dysfunction. Anti-NR2 antibodies were significantly correlated with BDI scores; patients with BDI-II scores of > or =14 had higher serum levels of anti-NR2 antibodies (P = 0.005, 95% confidence interval 0.83, 4.31), and there was a trend toward higher anti-NR2 antibody levels among patients who fulfilled the DSM-IV criteria for major depression. CONCLUSION: Serum anti-NR2 antibodies are associated with depressive mood but not with cognitive dysfunction in SLE at a given time point. Larger longitudinal studies are needed to address the possible association between anti-NR2 antibodies and depression in SLE.

Adult↗
PubMed2006

Effect of metabotropic glutamate receptor 3 genotype on N-acetylaspartate measures in the dorsolateral prefrontal cortex.

OBJECTIVE: This study was carried out to confirm prior evidence of an effect of a single nucleotide polymorphism (SNP) in the metabotropic glutamate receptor 3 (GRM3) gene (a putative risk factor for schizophrenia) on measures of N-acetylaspartate in healthy comparison subjects. METHOD: Fifty-four carefully screened healthy volunteers genotyped at SNP rs6465084 underwent magnetic resonance spectroscopic imaging (MRSI) at 3 T and selected neuropsychological testing. RESULTS: The A/A genotype group exhibited a significant reduction of N-acetylaspartate/creatine levels in the right dorsolateral prefrontal cortex compared to the G carriers. A tendency in the same direction was seen in the left dorsolateral prefrontal cortex and in the white matter adjacent to the prefrontal cortex. CONCLUSIONS: These findings provide further evidence that GRM3 affects prefrontal function and that variation in GRM3, monitored by SNP rs6465084, affects GRM3 function.

Aspartic Acid↗
PubMed2006

Therapeutic potential of positive AMPA receptor modulators in the treatment of neuropsychiatric disorders.

Drugs that potentiate the activity of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor cause a complex cascade of consequences in experimental models, ranging from enhancement of long-term potentiation to induction of neurotrophic factors. Animal studies characterising the pharmacological and behavioural effects of these substances have provided the rationale for several initial attempts to use these drugs in neuropsychiatric clinical settings. Applications in schizophrenia, Alzheimer's disease and mild cognitive impairment have been initiated. Other trials with these compounds include the treatment of Fragile X syndrome, and possible future applications may be in the field of Parkinson's disease. The literature published to date is limited mostly to small phase I or II trials, so there is no conclusive evidence for or against the use of these drugs. Substantial questions remain concerning which compounds to use, in what dose, for what condition and for how long.

Animals↗
PubMed2005

Functional, structural, and metabolic abnormalities of the hippocampal formation in Williams syndrome.

Williams syndrome (WS), caused by microdeletion of some 21 genes on chromosome 7q11.23, is characterized by dysmorphic features, mental retardation or learning difficulties, elastin arteriopathy, and striking neurocognitive and social-behavioral abnormalities. Recent studies of murine knockouts of key genes in the microdeleted region, LIM kinase 1 (LIMK1) and cytoplasmatic linker protein 2 (CYLN2), demonstrated significant functional and metabolic abnormalities, but grossly normal structure, in the hippocampal formation (HF). Furthermore, deficits in spatial navigation and long-term memory, major cognitive domains dependent on hippocampal function, have been described in WS. We used multimodal neuroimaging to characterize hippocampal structure, function, and metabolic integrity in 12 participants with WS and 12 age-, sex-, and IQ-matched healthy controls. PET and functional MRI studies showed profound reduction in resting blood flow and absent differential response to visual stimuli in the anterior HF in WS. Spectroscopic measures of N-acetyl aspartate, considered a marker of synaptic activity, were reduced. Hippocampal size was preserved, but subtle alterations in shape were present. These data demonstrate abnormalities in HF in WS in agreement with murine models, implicate LIMK1 and CYLN2 in human hippocampal function, and suggest that hippocampal dysfunction may contribute to neurocognitive abnormalities in WS.

Adult↗
PubMed2004

Nicotine-induced dopamine release in primates measured with [11C]raclopride PET.

Nicotine-induced dopamine (DA) release constitutes a pharmacological probe of the DA system that has potential use in patients with schizophrenia, who have abnormally elevated DA release after amphetamine administration and possibly abnormalities in nicotinic signaling. We performed positron emission tomography studies in five rhesus monkeys that received i.v. nicotine doses ranging from 0.01 to 0.06 mg/kg. [(11)C]raclopride was administered with either a bolus plus constant infusion or with paired bolus injections. The dynamics of D-2-binding potential (BP) after nicotine administration were studied and compared to amphetamine. Nicotine caused a significant albeit small reduction (5%, p<0.03) in BP, regardless of methodology of tracer administration. This effect disappeared 2.5 h after nicotine administration. Amphetamine caused much larger and prolonged displacement of [(11)C]raclopride as compared to nicotine. There was no correlation between changes in BP and nicotine dose or plasma level. Regional differences in the nicotine effect within the basal ganglia were not found. Our data are consistent with the increase in DA detected with microdialysis in animals after acute nicotine administration, however, a larger effect size would be desirable to attempt studies comparing human smokers with and without schizophrenia.

Amphetamine↗
PubMed2003

Comparison of cognitive performances during a placebo period and an atypical antipsychotic treatment period in schizophrenia: critical examination of confounds.

Although previous studies report cognitive improvement following atypical antipsychotic administration in schizophrenia (SC), few placebo-controlled within-subject studies with examination of confounds (symptom reduction, cooperation, learning, and outliers) have been reported. The present study examines the effects of atypicals and confounds upon cognition in SC. The hypothesis tested was that relative to placebo, atypicals as a general class of medication would elicit cognitive improvement in SC. In all, 19 patients with SC (15 males) completed the double-blind, counterbalanced, randomized within-subject study of the effects of atypical antipsychotics (risperidone, clozapine, olanzapine, or quetiapine) vs placebo administration upon cognitive performance in the domains of executive function, attention, memory, language, visual perception, and general intellect. Significant cognitive improvement during atypical antipsychotic administration relative to placebo withdrawal occurred in most cognitive domains with robust improvements in intelligence (p=0.001), memory (p=0.0009), and fluency (p <0.002) even after outliers and unmotivated performances were excluded. These findings suggest that relative to placebo withdrawal, atypicals improve cognitive performance in SC. However, this finding may not be specific to atypicals, since analogous studies of typicals have not been performed.

Adult↗
PubMed2003

Single-cue delay and trace classical conditioning in schizophrenia.

BACKGROUND: Classical conditioning provides a means of addressing mechanisms of learning and can therefore help understand the pathophysiology of memory alteration in schizophrenia. METHODS: Single cue delay and trace eyeblink conditioning were used in patients with schizophrenia and matched normal control subjects to explore, respectively, cerebellar and hippocampal integrity during learning. We measured percent of conditioned (CRs) and unconditioned responses (URs), their amplitude, and onset and peak latencies. We also accounted for spontaneous blink rates and stimulus-induced responses before learning. RESULTS: During delay conditioning, patients showed CRs with longer onset and peak latencies and improved efficiency compared to normal volunteers without there being differences between patients and normal control subjects in the percentage of CRs. During trace conditioning, neither group showed an increase in CRs as a function of conditioned stimulus-unconditioned stimulus pairings, in part because the level of spontaneous blink rates exceeded the level of CRs; however, patients with schizophrenia showed increased responding 150-400 msec after the conditioned stimulus and in the last 100-150 msec before the unconditioned stimulus, whereas normal control subjects showed only the latter type of responses. The former type of response was more frequent in patients with schizophrenia even before either trace or delay conditioning. CONCLUSIONS: These results suggest integrity of cerebellar mechanisms underlying conditioning, although the altered timing of CRs in patients may indicate differences in the modulation of such responses. Both the greater CR onset latency during delay and the presence of early nonadaptive responses during trace are compatible with the pattern of responding seen in animals with hippocampal damage.

Blinking↗
PubMed2003

Complexity of prefrontal cortical dysfunction in schizophrenia: more than up or down.

OBJECTIVE: Numerous neuroimaging studies have examined the function of the dorsolateral prefrontal cortex in schizophrenia; although abnormalities usually are identified, it is unclear why some studies find too little activation and others too much. The authors' goal was to explore this phenomenon. METHOD: They used the N-back working memory task and functional magnetic resonance imaging at 3 T to examine a group of 14 patients with schizophrenia and a matched comparison group of 14 healthy subjects. RESULTS: Patients' performance was significantly worse on the two-back working memory task than that of healthy subjects. However, there were areas within the dorsolateral prefrontal cortex of the patients that were more active and areas that were less active than those of the healthy subjects. When the groups were subdivided on the basis of performance on the working memory task into healthy subjects and patients with high or low performance, locales of greater prefrontal activation and locales of less activation were found in the high-performing patients but only locales of underactivation were found in the low-performing patients. CONCLUSIONS: These findings suggest that patients with schizophrenia whose performance on the N-back working memory task is similar to that of healthy comparison subjects use greater prefrontal resources but achieve lower accuracy (i.e., inefficiency) and that other patients with schizophrenia fail to sustain the prefrontal network that processes the information, achieving even lower accuracy as a result. These findings add to other evidence that abnormalities of prefrontal cortical function in schizophrenia are not reducible to simply too much or too little activity but, rather, reflect a compromised neural strategy for handling information mediated by the dorsolateral prefrontal cortex.

Achievement↗
PubMed2002

Preliminary experience with an ampakine (CX516) as a single agent for the treatment of schizophrenia: a case series.

We used L-(quinoxalin-6-ylcarbonyl)piperidine (CX516) (a modulator of the alpha-amino-3-hydroxy-5-methyl-4-isoxasole propionic acid (AMPA) receptor) as a sole agent in a double blind placebo-controlled design in a small series of patients with schizophrenia who were partially refractory to treatment with traditional neuroleptics. The study entailed weekly increments in doses of CX516, from 300 mg tid for week 1 up to 900 mg tid on week 4. Patients were followed with clinical ratings, neuropsychological testing, and were monitored for adverse events. Four patients received 2 to 4 weeks of CX516, two received placebo and two withdrew during the placebo phase. Adverse events associated with drug administration were transient and included leukopenia in one patient and elevation in liver enzymes in another. No clear improvement in psychosis or in cognition was observed over the course of the study. CX516 at the doses tested did not appear to yield dramatic effects as a sole agent, but inference from this study is limited.

Adult↗