Periodontitis as a Risk Factor for Alzheimer's Disease: The Experimental Journey So Far, with Hope of Therapy.

Periodontitis and Alzheimer's disease (AD) exist globally within the adult population. Given that the risk of AD incidence doubles within 10 years from the time of periodontal disease diagnosis, there is a window of opportunity for slowing down or preventing AD by risk-reduction-based intervention. Literature appraisal on the shared risk factors of these diseases suggests a shift to a healthy lifestyle would be beneficial. Generalised (chronic) periodontitis with an established dysbiotic polymicrobial aetiology affects the tooth supporting tissues with eventual tooth loss. The cause of AD remains unknown, however two neurohistopathological lesions - amyloid-beta plaques and neurofibrillary tangles, together with the clinical history, provide AD diagnosis at autopsy. Historically, prominence was given to the two hallmark lesions but now emphasis is placed on cerebral inflammation and what triggers it. Low socioeconomic status promotes poor lifestyles that compromise oral and personal hygiene along with reliance on poor dietary intake. Taken together with advancing age and a declining immune protection, these risk factors may negatively impact on periodontitis and AD. These factors also provide a tangible solution to controlling pathogenic bacteria indigenous to the oral and gastrointestinal tract microbioes in vulnerable subjects. The focus here is on Porphyromonas gingivalis, one of several important bacterial pathogens associated with both periodontitis and AD. Recent research has enabled advances in our knowledge of the armoury of P. gingivalis via reproduction of all clinical and neuropathological hallmark lesions of AD and chronic periodontal disease in vitro and in vivo experimental models, thus paving the way for better future management.

An evaluation of the molecular mode of action of trans-resveratrol in the Porphyromonas gingivalis lipopolysaccharide challenged neuronal cell model.

Porphyromonas gingivalis triggers a range of innate immune responses in the host that may contribute to the development of periodontitis and dementing diseases including Alzheimer's disease (AD). This study aimed to assess the mode of action of trans-resveratrol in modulating the P. gingivalis lipopolysaccharide (PgLPS) induced metabolic inflammation in a neuronal cell model. Confluent IMR-32 neuroblastoma cells were treated with trans-resveratrol from Polygonum cuspidatum in the presence or absence of PgLPS. The abundance of messenger ribo-nucleic acid (mRNA) transcripts of a panel of 92 genes was quantitatively assessed through targeted transcriptome profiling technique and the biochemical pathways affected were identified through Ingenuity Pathway Analysis. Gene expression analysis revealed that trans-resveratrol down-regulated the mRNA of multiple gene markers including growth factors, transcription factors, kinases, trans-membrane receptors, cytokines and enzymes that were otherwise activated by PgLPS treatment of IMR-32 neuroblastoma cells. Pathway analysis demonstrated that the cellular oxidative stress caused by the activation of phosphoinositide-3-kinase/Akt1 (PI3K/Akt1) pathway that leads to the production of reactive oxygen species (ROS), chronic inflammatory response induced by the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) pathway and nutrient utilization pathways were favourably modulated by trans-resveratrol in the PgLPS challenged IMR-32 cells. This study demonstrates the potential of trans-resveratrol as a bioactive compound with multiple modes of intracellular action further supporting its therapeutic application in neuroinflammatory diseases.

Progression from selective to general involvement of hippocampal subfields in schizophrenia.

Volume deficits of the hippocampus in schizophrenia have been consistently reported. However, the hippocampus is anatomically heterogeneous; it remains unclear whether certain portions of the hippocampus are affected more than others in schizophrenia. In this study, we aimed to determine whether volume deficits in schizophrenia are confined to specific subfields of the hippocampus and to measure the subfield volume trajectories over the course of the illness. Magnetic resonance imaging scans were obtained from Data set 1: 155 patients with schizophrenia (mean duration of illness of 7 years) and 79 healthy controls, and Data set 2: an independent cohort of 46 schizophrenia patients (mean duration of illness of 18 years) and 46 healthy controls. In addition, follow-up scans were collected for a subset of Data set 1. A novel, automated method based on an atlas constructed from ultra-high resolution, post-mortem hippocampal tissue was used to label seven hippocampal subfields. Significant cross-sectional volume deficits in the CA1, but not of the other subfields, were found in the schizophrenia patients of Data set 1. However, diffuse cross-sectional volume deficits across all subfields were found in the more chronic and ill schizophrenia patients of Data set 2. Consistent with this pattern, the longitudinal analysis of Data set 1 revealed progressive illness-related volume loss (~2-6% per year) that extended beyond CA1 to all of the other subfields. This decline in volume correlated with symptomatic worsening. Overall, these findings provide converging evidence for early atrophy of CA1 in schizophrenia, with extension to other hippocampal subfields and accompanying clinical sequelae over time.

Prevalence and predictors of early gestational weight gain associated with obesity risk in a diverse Australian antenatal population: a cross-sectional study.

BACKGROUND: Excess gestational weight gain (GWG) leads to adverse short- and long-term consequences for women and their offspring. Evidence suggests that excess GWG in early pregnancy may be particularly detrimental, contributing to the intergenerational cycle of obesity. The primary outcome was to investigate the prevalence and predictors of excess GWG in early pregnancy, and if women understand the risks to themselves and their offspring stratified by maternal body mass index (BMI). METHODS: This was a secondary analysis (n = 2131) of a cross-sectional study (n = 2338) conducted over 6 months in 2015 of pregnant women attending antenatal clinics at four maternity hospitals across Sydney, Australia before 22 completed weeks gestation An self-completed questionnaire was used to investigate knowledge of expected weight gain in pregnancy, understanding of risks associated with excess GWG, self-reported anthropometric measures and socio-demographic data. RESULTS: One third (34.2%) of women gained weight in excess of the recommendations by 22 completed weeks gestation. Women who were overweight (OR: 1.69, 95% CI: 1.33-2.14) or obese (OR: 1.64, 95% CI: 1.20-2.24) pre-pregnancy were more likely to gain excess weight in early pregnancy compared to normal weight women; as were women from lower socio-economic areas (OR: 1.89, 95% CI: 1.49-2.41). Half (51%) the women were unsure about the effect of excess GWG on their baby; 11% did not believe that excess GWG would affect the weight of the baby and 14% did not believe that excess GWG would affect longer term outcomes for their baby. Women who gained weight above the recommendations were significantly more likely to believe that excessive GWG in pregnancy would not have any adverse future effect on health outcomes or weight of their baby. CONCLUSIONS: The women at particular risk of excess early GWG are those who are overweight and obese and/or residing in lower socio-economic areas. These women need to be targeted for appropriate counselling preconception or in early pregnancy. Given the significant adverse outcomes associated with excess GWG in early pregnancy, preconception or early pregnancy counselling with respect to GWG and intervention research regarding best approach remains a public health priority.

Developing an ecologically relevant heterogeneous biofilm model for dental-unit waterlines.

This study monitored the biodiversity of microbes cultured from a heterogeneous biofilm which had formed on the lumen of a section of dental waterline tubing over a period of 910 days. By day 2 bacterial counts on the outlet-water showed that contamination of the system had occurred. After 14 days, a biofilm comparable to that of clinical waterlines, consisting of bacteria, fungi and amoebae had formed. This showed that the proprietary silver coating applied to the luminal surface of the commercial waterline tubing failed to prevent biofilm formation. Molecular barcoding of isolated culturable microorganisms showed some degree of the diversity of taxa in the biofilm, including the opportunistic pathogen Legionella pneumophila. Whilst the system used for isolation and identification of contaminating microorganisms may underestimate the diversity of organisms in the biofilm, their similarity to those found in the clinical environment makes this a promising test-bed for future biocide testing.

Oral flora in acute stroke patients: A prospective exploratory observational study.

OBJECTIVE: To describe the bacterial profile of the oral flora during the first 2 weeks following a stroke, examining changes in the condition of the oral cavity and infections. BACKGROUND: Dysphagia is common after a stroke and can lead to aspiration pneumonia. Oral flora changes associated with stroke have been implicated as a possible source of bacteria that can cause systemic infections. MATERIALS AND METHODS: Seventy-seven participants were recruited over a period of 9 months. Fifty participants had a complete set of swabs from four different oral sites and a saliva sample taken at three time points over a 14-day period. Molecular identification of bacteria was performed on the pooled DNA extracted. RESULTS: A total of 103 bacterial phylotypes were identified, 29 of which were not in the Human Oral Microbiome Database (HOMD). Fourteen of the twenty most common bacterial phylotypes found in the oral cavity were Streptococcal species with Streptococcus salivarius being the most common. The condition of the oral cavity worsened during the study period. Fifteen (30%) patients had at least one infection. CONCLUSIONS: There appears to be huge diversity of bacterial organisms in the oral cavity of stroke patients, and as most phylotypes identified were only found in one or two participants, no particular patterns linked to infection or the condition of the oral cavity could be discerned.

Nonlinear least squares regression for single image scanning electron microscope signal-to-noise ratio estimation.

A new method based on nonlinear least squares regression (NLLSR) is formulated to estimate signal-to-noise ratio (SNR) of scanning electron microscope (SEM) images. The estimation of SNR value based on NLLSR method is compared with the three existing methods of nearest neighbourhood, first-order interpolation and the combination of both nearest neighbourhood and first-order interpolation. Samples of SEM images with different textures, contrasts and edges were used to test the performance of NLLSR method in estimating the SNR values of the SEM images. It is shown that the NLLSR method is able to produce better estimation accuracy as compared to the other three existing methods. According to the SNR results obtained from the experiment, the NLLSR method is able to produce approximately less than 1% of SNR error difference as compared to the other three existing methods.

Performance of signal-to-noise ratio estimation for scanning electron microscope using autocorrelation Levinson-Durbin recursion model.

A new technique to quantify signal-to-noise ratio (SNR) value of the scanning electron microscope (SEM) images is proposed. This technique is known as autocorrelation Levinson-Durbin recursion (ACLDR) model. To test the performance of this technique, the SEM image is corrupted with noise. The autocorrelation function of the original image and the noisy image are formed. The signal spectrum based on the autocorrelation function of image is formed. ACLDR is then used as an SNR estimator to quantify the signal spectrum of noisy image. The SNR values of the original image and the quantified image are calculated. The ACLDR is then compared with the three existing techniques, which are nearest neighbourhood, first-order linear interpolation and nearest neighbourhood combined with first-order linear interpolation. It is shown that ACLDR model is able to achieve higher accuracy in SNR estimation.

Image signal-to-noise ratio estimation using adaptive slope nearest-neighbourhood model.

A new technique based on nearest neighbourhood method is proposed. In this paper, considering the noise as Gaussian additive white noise, new technique single-image-based estimator is proposed. The performance of this new technique such as adaptive slope nearest neighbourhood is compared with three of the existing method which are original nearest neighbourhood (simple method), first-order interpolation method and shape-preserving piecewise cubic hermite autoregressive moving average. In a few cases involving images with different brightness and edges, this adaptive slope nearest neighbourhood is found to deliver an optimum solution for signal-to-noise ratio estimation problems. For different values of noise variance, the adaptive slope nearest neighbourhood has highest accuracy and less percentage estimation error. Being more robust with white noise, the new proposed technique estimator has efficiency that is significantly greater than those of the three methods.

Signal-to-noise ratio enhancement on SEM images using a cubic spline interpolation with Savitzky-Golay filters and weighted least squares error.

A new technique based on cubic spline interpolation with Savitzky-Golay smoothing using weighted least squares error filter is enhanced for scanning electron microscope (SEM) images. A diversity of sample images is captured and the performance is found to be better when compared with the moving average and the standard median filters, with respect to eliminating noise. This technique can be implemented efficiently on real-time SEM images, with all mandatory data for processing obtained from a single image. Noise in images, and particularly in SEM images, are undesirable. A new noise reduction technique, based on cubic spline interpolation with Savitzky-Golay and weighted least squares error method, is developed. We apply the combined technique to single image signal-to-noise ratio estimation and noise reduction for SEM imaging system. This autocorrelation-based technique requires image details to be correlated over a few pixels, whereas the noise is assumed to be uncorrelated from pixel to pixel. The noise component is derived from the difference between the image autocorrelation at zero offset, and the estimation of the corresponding original autocorrelation. In the few test cases involving different images, the efficiency of the developed noise reduction filter is proved to be significantly better than those obtained from the other methods. Noise can be reduced efficiently with appropriate choice of scan rate from real-time SEM images, without generating corruption or increasing scanning time.

Risk Assessment for the Spread of Serratia marcescens Within Dental-Unit Waterline Systems Using Vermamoeba vermiformis.

Vermamoeba vermiformis is associated with the biofilm ecology of dental-unit waterlines (DUWLs). This study investigated whether V. vermiformis is able to act as a vector for potentially pathogenic bacteria and so aid their dispersal within DUWL systems. Clinical dental water was initially examined for Legionella species by inoculating it onto Legionella selective-medium plates. The molecular identity/profile of the glassy colonies obtained indicated none of these isolates were Legionella species. During this work bacterial colonies were identified as a non-pigmented Serratia marcescens. As the water was from a clinical DUWL which had been treated with Alpron™, this prompted the question as to whether S. marcescens had developed resistance to the biocide. Exposure to Alpron™ indicated that this dental biocide was effective, under laboratory conditions, against S. marcescens at up to 1 × 10(8) colony forming units/millilitre (cfu/ml). V. vermiformis was cultured for 8 weeks on cells of S. marcescens and Escherichia coli. Subsequent electron microscopy showed that V. vermiformis grew equally well on S. marcescens and E. coli (P = 0.0001). Failure to detect the presence of S. marcescens within the encysted amoebae suggests that V. vermiformis is unlikely to act as a vector supporting the growth of this newly isolated, nosocomial bacterium.

Porphyromonas gingivalis Periodontal Infection and Its Putative Links with Alzheimer's Disease.

Periodontal disease (PD) and Alzheimer's disease (AD) are inflammatory conditions affecting the global adult population. In the pathogenesis of PD, subgingival complex bacterial biofilm induces inflammation that leads to connective tissue degradation and alveolar bone resorption around the teeth. In health, junctional epithelium seals the gingiva to the tooth enamel, thus preventing bacteria from entering the gingivae. Chronic PD involves major pathogens (Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia) which have an immune armoury that can circumvent host's immune surveillance to create and maintain an inflammatory mediator rich and toxic environment to grow and survive. The neurodegenerative condition, AD, is characterised by poor memory and specific hallmark proteins; periodontal pathogens are increasingly being linked with this dementing condition. It is therefore becoming important to understand associations of periodontitis with relevance to late-onset AD. The aim of this review is to discuss the relevance of finding the keystone periodontal pathogen P. gingivalis in AD brains and its plausible contribution to the aetiological hypothesis of this dementing condition.

Informed consent for human genetic and genomic studies: a systematic review.

As genetic and genomic studies grow in scale, there are ethical concerns related to the collection and use of genetic information. The emergence of large public databases potentially redefine the terms of participation in genetic and genomic research, and suggests the changing application of traditional ethical principles such as privacy or consent. For this study, we wanted to see whether such developments are reflected in the informed consent processes in human genetic and genomic studies. Therefore, we performed a systematic review of the empirical studies that examined informed consent involving large genetic databases in human genetic and genomic studies, grouped the identified issues related to the different stakeholders (including subjects, researchers, and institutional review boards) and discussed the limitations and implications of these findings. Major themes related to the place of bioethical considerations, procured tissues, people involved, process of informed consent and study procedures. Frequently raised issues included confidentiality of participants, documentation of informed consent, public attitudes, future use of participant samples or data, and disclosure of results. Awareness and attention to these bioethical issues as well as assiduousness in managing these concerns in genetic/genomic research would further strengthen and safeguard the rights, safety and well-being of genetic research participants.

Increased body mass index makes an impact on brain white-matter integrity in adults with remitted first-episode mania.

BACKGROUND: Obesity is increasingly prevalent in bipolar disorder (BD) but data about the impact of elevated body mass index (BMI) on brain white-matter integrity in BD are sparse. Based on extant literature largely from structural magnetic resonance imaging (MRI) studies, we hypothesize that increased BMI is associated with decreased fractional anisotropy (FA) in the frontal, temporal, parietal and occipital brain regions early in the course of BD. METHOD: A total of 26 euthymic adults (12 normal weight and 14 overweight/obese) with remitted first-episode mania (FEM) and 28 controls (13 normal weight and 15 overweight/obese) matched for age, handedness and years of education underwent structural MRI and diffusion tensor imaging scans. RESULTS: There are significant effects of diagnosis by BMI interactions observed especially in the right parietal lobe (adjusted F(1,48) = 5.02, p = 0.030), occipital lobe (adjusted F(1,48) = 10.30, p = 0.002) and temporal lobe (adjusted F(1,48) = 7.92, p = 0.007). Specifically, decreased FA is found in the right parietal (F(1,48) = 5.864, p = 0.023) and occipital lobes (F(1,48) = 4.397, p = 0.047) within overweight/obese patients compared with normal-weight patients with FEM. Compared with overweight/obese controls, decreased FA is observed in right parietal (F(1,48) = 6.708, p = 0.015), temporal (F(1,48) = 10.751, p = 0.003) and occipital (F(1,48) = 9.531, p = 0.005) regions in overweight/obese patients with FEM. CONCLUSIONS: Our findings suggest that increased BMI affects temporo-parietal-occipital brain white-matter integrity in FEM. This highlights the need to further elucidate the relationship between obesity and other neural substrates (including subcortical changes) in BD which may clarify brain circuits subserving the association between obesity and clinical outcomes in BD.

Signal-to-noise ratio estimation on SEM images using cubic spline interpolation with Savitzky-Golay smoothing.

A new technique based on cubic spline interpolation with Savitzky-Golay noise reduction filtering is designed to estimate signal-to-noise ratio of scanning electron microscopy (SEM) images. This approach is found to present better result when compared with two existing techniques: nearest neighbourhood and first-order interpolation. When applied to evaluate the quality of SEM images, noise can be eliminated efficiently with optimal choice of scan rate from real-time SEM images, without generating corruption or increasing scanning time.

The association between bone mineral density and periodontitis in Korean adults (KNHANES 2008-2010).

OBJECTIVES: This study investigated the association between bone mineral density (BMD) and periodontitis in a representative sample of Korean adults. MATERIAL AND METHODS: Of 36 188 individuals who participated in the Korea National Health and Nutrition Examination Survey in 2008, 2009, and 2010, 9977 participants aged ≥40 years were included in this cross-sectional study. The associations of BMD of lumbar spine, total femur, and femoral neck with periodontitis were investigated using logistic regression analysis. Additionally, dose-response relationships with BMD divided into quintiles and the association between osteoporosis and periodontitis were investigated. RESULTS: With the set of Community Periodontal Index (CPI) ≥ 3 as a dependent variable, logistic regression analysis revealed that a decrease of BMD was significantly associated with higher odds of periodontitis [range of adjusted odds ratios (AORs); 1.15-1.20, P < 0.001 for all BMD sites]. Similarly, these associations were also found in the CPI 4 model. With regard to dose-response relations, the lower the BMD quintile, the higher the AORs appeared with statistical significance in the CPI ≥ 3 model. (P for trend < 0.001) Participants with osteoporosis had 2.26 and 1.91 times higher odds for CPI ≥ 3 and CPI 4, respectively, than those with normal BMD, indicating a significant association between the two diseases. CONCLUSIONS: Our results suggest that BMD is significantly associated with periodontitis.

Monitoring dental-unit-water-line output water by current in-office test kits.

The importance of monitoring contamination levels in the output water of dental-unit-water-lines (DUWLs) is essential as they are prone to developing biofilms that may contaminate water that is used to treat patients, with opportunistic pathogens such as species of Legionella, Pseudomonas and others. Dentists and practice staff are also at risk of being infected by means of cross-infection due to aerosols generated from DUWL water. The unit of measurement for the microbial contamination of water by aerobic mesophilic heterotrophic bacteria is the colony-forming unit per millilitre (cfu/ml) of water. The UK has its own guidelines set by the Department of Health for water discharged from DUWL to be between 100 and 200 cfu/ml of water. The benchmark or accepted standard laboratory test is by microbiological culture on R2A agar plates. However, this is costly and not convenient for routine testing in dental practices. A number of commercial indicator tests are used in dental surgeries, but they were not developed for the dental market and serve only to indicate gross levels of contamination when used outside of the manufacturer's recommended incubation period. The aim of this article is to briefly review the universal problem of DUWL contamination with microbial biofilms and to update dental professionals on the availability of currently available commercial in-office monitoring systems for aerobic mesophilic heterotrophic bacteria and to discuss their limitations for testing water samples in assuring compliance with recommended guidelines.

Carotid intima media thickness and high sensitivity C-reactive protein as markers of cardiovascular risk in a malaysian population.

INTRODUCTION: Carotid intima media thickness (CIMT) being a cost effective and easily performed technique is useful in the detection of subclinical atherosclerosis and has been shown to be a prognosticator of cardiovascular events. The primary objective of this study was to obtain the distribution of CIMT measurements, highly sensitive C reactive protein (hs-CRP) and assessing health awareness and attitudes of the Malaysian population at cardiovascular disease (CVD) risk and not receiving lipid lowering agents. Secondarily the study sought to assess the significance of the relationship between these measurements against various patient characteristics. METHODS: Measurements of CIMT are obtained by ultrasonography of 12 sites within the common carotid artery was recorded for 123 subjects from a single centre tertiary hospital of Malaysia who had two or more CVD risk factors but were not receiving lipid lowering therapy. CVD risk factors and lipid and glucose profiles were analyzed with respect to distribution of CIMT and high-sensitivity Creactive protein (hs-CRP) values. RESULTS: The mean-max CIMT was 0.916±0.129mm (minimum 0.630mm, maximum 1.28mm) and the mean-mean CIMT was 0.743±0.110mm (minimum 0.482mm, maximum 1.050mm) and mean hs-CRP was 0.191mg/dL (minimum 0.030mg/dL, maximum 5.440mg/dL). Multivariate analyses confirmed a significant association between increasing CIMT and increasing age, total and low density lipoprotein cholesterol while log-transformed hs-CRP levels showed significant association with increasing body mass index, waist circumference, high blood glucose and triglyceride levels. Our patients had good health awareness on CVD. CONCLUSION: Newly defined CIMT measurements and hs-CRP levels may be useful adjunctive tools to screen for atherosclerosis in the Malaysian population. It may help in refining risk stratification on top of traditional clinical assessment.

MIR137 polygenic risk for schizophrenia and ephrin-regulated pathway: Role in lateral ventricles and corpus callosum volume.

Background/Objective. Enlarged lateral ventricle (LV) volume and decreased volume in the corpus callosum (CC) are hallmarks of schizophrenia (SZ). We previously showed an inverse correlation between LV and CC volumes in SZ, with global functioning decreasing with increased LV volume. This study investigates the relationship between LV volume, CC abnormalities, and the microRNA MIR137 and its regulated genes in SZ, because of MIR137's essential role in neurodevelopment. Methods. Participants were 1224 SZ probands and 1466 unaffected controls from the GENUS Consortium. Brain MRI scans, genotype, and clinical data were harmonized across cohorts and employed in the analyses. Results. Increased LV volumes and decreased CC central, mid-anterior, and mid-posterior volumes were observed in SZ probands. The MIR137-regulated ephrin pathway was significantly associated with CC:LV ratio, explaining a significant proportion (3.42 %) of CC:LV variance, and more than for LV and CC separately. Other pathways explained variance in either CC or LV, but not both. CC:LV ratio was also positively correlated with Global Assessment of Functioning, supporting previous subsample findings. SNP-based heritability estimates were higher for CC central:LV ratio (0.79) compared to CC or LV separately. Discussion. Our results indicate that the CC:LV ratio is highly heritable, influenced in part by variation in the MIR137-regulated ephrin pathway. Findings suggest that the CC:LV ratio may be a risk indicator in SZ that correlates with global functioning.

Amygdala-hippocampal shape and cortical thickness abnormalities in first-episode schizophrenia and mania.

BACKGROUND: Abnormalities in cortical thickness and subcortical structures have been studied in schizophrenia but little is known about corresponding changes in mania and brain structural differences between these two psychiatric conditions, especially early in the stage of the illness. In this study we aimed to compare cortical thickness and shape of the amygdala-hippocampal complex in first-episode schizophrenia (FES) and mania (FEM). Method Structural magnetic resonance imaging (MRI) was performed on 28 FES patients, 28 FEM patients and 28 healthy control subjects who were matched for age, gender and handedness. RESULTS: Overall, the shape of the amygdala was deformed in both patient groups, relative to controls. Compared to FEM patients, FES patients had significant inward shape deformation in the left hippocampal tail, right hippocampal body and a small region in the right amygdala. Cortical thinning was more widespread in FES patients, with significant differences found in the temporal brain regions when compared with FEM and controls. CONCLUSIONS: Significant differences were observed between the two groups of patients with FES and FEM in terms of the hippocampal shape and cortical thickness in the temporal region, highlighting that distinguishable brain structural changes are present early in the course of schizophrenia and mania.