Dataset Information

COMT, neuropsychological function and brain structure in schizophrenia: a systematic review and neurobiological interpretation.

ABSTRACT: BACKGROUND: Endophenotypes in genetic psychiatry may increase our understanding of the molecular mechanisms underlying disease risk and its manifestations. We sought to investigate the link between neuropsychological impairments and brain structural abnormalities associated with the COMT Val(158)Met polymorphism in patients with schizophrenia to improve understanding of the pathophysiology of this disorder. METHODS: We performed a systematic review using studies identified in PubMed and MEDLINE (from the date of the first available article to July 2012). Our review examined evidence of an association between the COMT Val(158)Met polymorphism and both neuropsychological performance and brain structure in patients with psychosis, in their relatives and in healthy individuals (step 1). The review also explored whether the neuropsychological tasks and brain structures identified in step 1 met the criteria for an endophenotype (step 2). Then we evaluated evidence that the neuropsychological endophenotypes identified in step 2 are associated with the brain structure endophenotypes identified in that step (step 3). Finally, we propose a neurobiological interpretation for this evidence. RESULTS: A poorer performance on the n-back task and the Continuous Performance Test (CPT) and smaller temporal and frontal brain areas were associated with the COMT Val allele in patients with schizophrenia and their relatives and met most of the criteria for an endophenotype. It is possible that the COMT Val(158)Met polymorphism therefore contributes to the development of these neuropsychological and brain structural endophenotypes of schizophrenia, in which the prefrontal cortex may represent the neural substrate underlying both n-back and CPT performances. LIMITATIONS: The association between a single genetic variant and an endophenotype does not necessarily imply a causal relationship between them. CONCLUSION: This evidence and the proposed interpretation contribute to explain, at least in part, the biological substrate of 4 important endophenotypes that characterize schizophrenia.

SUBMITTER: Ira E

PROVIDER: S-EPMC3819150 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

COMT, neuropsychological function and brain structure in schizophrenia: a systematic review and neurobiological interpretation.

Ira Elisa E Zanoni Martina M Ruggeri Mirella M Dazzan Paola P Tosato Sarah S

Journal of psychiatry & neuroscience : JPN 20131101 6

<h4>Background</h4>Endophenotypes in genetic psychiatry may increase our understanding of the molecular mechanisms underlying disease risk and its manifestations. We sought to investigate the link between neuropsychological impairments and brain structural abnormalities associated with the COMT Val(158)Met polymorphism in patients with schizophrenia to improve understanding of the pathophysiology of this disorder.<h4>Methods</h4>We performed a systematic review using studies identified in PubMed ...[more]

PMID: 23527885

Similar Datasets

Project description:ObjectiveCognitive deficits are prominent in schizophrenia. Patients have an average score one standard deviation below normal on a broad spectrum of cognitive tests. It has been repeatedly noted, however, that 20%-25% of patients differ from this general pattern and score close to normal on neuropsychological testing. This study used brain morphometry to 1) identify brain abnormalities associated with more severe cognitive deficits and 2) help determine whether cognitively relatively intact patients perform better because they have less severe illness or because they have a different illness.MethodPatients were assigned to a neuropsychologically near normal (N=21) subgroup if they scored within 0.5 standard deviation of healthy comparison subjects (N=30) on four tests of attention and verbal and nonverbal working memory, and to a neuropsychologically impaired (N=54) group if they scored at least 1.0 standard deviation below that of comparison subjects. Subgroup assignments were confirmed with the California Verbal Learning Test and degraded-stimulus Continuous Performance Test. Volumes of ventricular compartments, hippocampus, amygdala, thalamus, cerebellum, and regional cortical gray and white matter were dependent variables. Differences among groups were evaluated by using linear mixed-model multivariate analyses with gender, age, and height as covariates.ResultsBoth neuropsychologically near normal and neuropsychologically impaired patients had markedly smaller gray matter and larger third ventricle volumes than healthy comparison subjects. Only neuropsychologically impaired patients, however, had significantly smaller white matter and larger lateral ventricle volumes than healthy comparison subjects.ConclusionsAlthough both neuropsychologically impaired and neuropsychologically near normal patients have marked neuropathology in their gray matter, the relative absence of white matter pathology in the neuropsychologically near normal group suggests the possibility of differences in the disease process.

Project description:ObjectiveTo investigate the effects of sport stacking on the overall cognition and brain function in patients with mild Alzheimer's disease (AD) and mild cognitive impairment (MCI).MethodsA single-blind randomized controlled design was performed using sport stacking for 30 min, 5 days/week for 12 weeks. Forty-eight subjects with mild AD or MCI were randomly divided into the sport stacking group (T-mAD = 12, T-MCI = 12) and the active control group (C-mAD = 11, C-MCI = 13). Auditory Verbal Learning Test (AVLT), Alzheimer's Disease Cooperative Study-Activities of Daily Living scale (ADCS-ADL), Geriatric Depression Scale (GDS-30), and Pittsburgh Sleep Quality Index (PSQI) were performed, the level of amyloid β-protein-40 (Aβ-40), Aβ-42, brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1(IGF-1), tumor necrosis factor-alpha (TNF-α), Interleukin-6 (IL-6), and soluble trigger receptor expressed on myeloid cells 2 (sTREM2) in plasma were tested, and brain functional connectivity in resting state and activation under finger movement task were analyzed by functional near-infrared spectroscopy (fNIRS).ResultsThirty-nine patients completed the trial. After 4 weeks, we found a significant increase in AVLT score in T-MCI (6.36 ± 5.08 vs. -1.11 ± 4.23, p = 0.004), and T-mAD group (4.60 ± 4.77 vs. -0.11 ± 2.89, p = 0.039). After 12 weeks, there was a significantly improved in AVLT (9.64 ± 4.90 vs. -0.33 ± 6.10, p = 0.002) and ADCS-ADL (3.36 ± 3.59 vs. -1.89 ± 2.71, p = 0.003) in T-MCI. There was a significant improvement in AVLT (5.30 ± 5.42 vs. 0.44 ± 2.40) in T-mAD (p < 0.05). Plasma levels of BDNF were upregulated in both T-MCI and T-mAD, and IGF-1 increased in T-MCI (P < 0.05) compared to the control groups. The functional connectivity in MCI patients between DLPFC.R and SCA.R, SMA.L, and SCA.R was decreased. In contrast, in mAD patients, the brain regional function connection was increased between DLPFC.R and Broca's.L. The activation of channel 36 located in the left primary somatosensory cortex was significantly increased after 12-week training, which was correlated with the improved AVLT and the increase of BDNF.ConclusionOur findings suggested that sport stacking is effective for patients with MCI and mild AD, possibly through increasing the expression of neuroprotective growth factors and enhancing neural plasticity to improve neurocognitive performance.Clinical trial registrationhttps://www.ClinicalTrials.gov, ChiCTR.org.cn, identifier: ChiCTR-2100045980.

Dataset Information

COMT, neuropsychological function and brain structure in schizophrenia: a systematic review and neurobiological interpretation.

Publications

COMT, neuropsychological function and brain structure in schizophrenia: a systematic review and neurobiological interpretation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets