1Mol. Psychiatry 2005 Jul 10: 631-6
TitleBrain-derived neurotrophic factor val66met polymorphism and volume of the hippocampal formation.
AbstractMagnetic resonance (MR) imaging studies have identified hippocampal structural alterations in the pathogenesis of schizophrenia. Brain-derived neurotrophic factor (BDNF) is one of the neurotrophins that is widely expressed in the hippocampal formation and has been implicated in the neurobiology of schizophrenia. Polymorphisms in the BDNF gene may therefore confer risk for schizophrenia through hippocampal pathogenesis and/or making the hippocampus more susceptible to environmental insults. In this study, we investigated whether val66met, a functional and abundant missense polymorphism in the coding region of the BDNF gene, was associated with the volume of the hippocampal formation in 19 patients with first-episode schizophrenia and 25 healthy volunteers. A total of 124 contiguous T1-weighted coronal MR images (slice thickness=1.5 mm) were acquired through the whole head using a 3D Fast SPGR IR PREP sequence on a 1.5 T GE imaging system. Volumes of the right and left hippocampal formation were measured manually by an operator blind to group status and genotype. All participants were genotyped for the BDNF val66met locus. Mixed model analyses revealed a main effect of BDNF val66met genotype such that in the combined sample of patients and healthy volunteers, val/val homozygotes (N=27) had larger volumes of the hippocampal formation compared to val/met heterozygotes (N=17). In separate analyses by group, however, val66met genotype accounted for a greater proportion of the variance in the volume of the hippocampal formation in patients compared to healthy volunteers. These findings implicate genetic involvement of BDNF in variation of human hippocampal volume and suggest that this effect may be greater among patients compared to healthy volunteers.
SCZ Keywordsschizophrenia, schizophrenics
2Schizophr. Res. 2007 Aug 94: 281-7
TitleCortisol levels in relation to hippocampal sub-regions in subjects with first episode schizophrenia.
AbstractThe etiology of hippocampal volumetric reductions in schizophrenia is largely unknown. In addition to genetic factors, environmental factors might also play a role. High levels of glucocorticoids are known to affect hippocampal volume in disorders such as Cushing's syndrome, but the relationship between cortisol and hippocampal volumes has not been studied in schizophrenia. We obtained diurnal salivary cortisol levels and MRI images to explore the link between cortisol levels and regional hippocampal volumes in healthy controls (N=29) and subjects with first episode schizophrenia (N=16) at the time of first admission. T1-weighted coronal MR images (slice thickness=1.5 mm) were acquired through the whole head using a 3D Fast SPGR IR PREP sequence on a 1.5 T GE imaging system. Using ANOVA, cumulative daily cortisol exposure calculated as area under the curve for each subject revealed significantly higher cortisol levels in the patient group [F(1,43)=4.4 p=0.04]. However, there were no statistically significant associations between the cortisol measures and regional hippocampal volumes in the subjects, except a trend level link between anterior hippocampal volume and cortisol in the positive direction, in parallel to previous findings in healthy adolescents. Our findings do not suggest a robust association between cortisol levels and hippocampal volumes in a first episode schizophrenia sample. Larger scale studies are needed to conclude a link between the two measures, yet it is possible that the negative association that was previously shown in other disorders may not apply to schizophrenia.
SCZ Keywordsschizophrenia, schizophrenics
3Front Hum Neurosci 2010 -1 3: 62
TitlePremorbid cognitive deficits in young relatives of schizophrenia patients.
AbstractNeurocognitive deficits in schizophrenia (SZ) are thought to be stable trait markers that predate the illness and manifest in relatives of patients. Adolescence is the age of maximum vulnerability to the onset of SZ and may be an opportune "window" to observe neurocognitive impairments close to but prior to the onset of psychosis. We reviewed the extant studies assessing neurocognitive deficits in young relatives at high risk (HR) for SZ and their relation to brain structural alterations. We also provide some additional data pertaining to the relation of these deficits to psychopathology and brain structural alterations from the Pittsburgh Risk Evaluation Program (PREP). Cognitive deficits are noted in the HR population, which are more severe in first-degree relatives compared to second-degree relatives and primarily involve psychomotor speed, memory, attention, reasoning, and social-cognition. Reduced general intelligence is also noted, although its relationship to these specific domains is underexplored. Premorbid cognitive deficits may be related to brain structural and functional abnormalities, underlining the neurobiological basis of this illness. Cognitive impairments might predict later emergence of psychopathology in at-risk subjects and may be targets of early remediation and preventive strategies. Although evidence for neurocognitive deficits in young relatives abounds, further studies on their structural underpinnings and on their candidate status as endophenotypes are needed.
SCZ Keywordsschizophrenia, schizophrenics