Resilient, undercontrolled, and overcontrolled personality types in Hong Kong youths and the association with mental health outcomes.

OBJECTIVE: This study aimed to investigate the relationship between RUO types and mental health in a youth sample in Hong Kong. BACKGROUND: Previous research has found that Resilient, Undercontrolled, and Overcontrolled (RUO) personality types derived from Big Five personality traits are associated with mental health outcomes. Most studies, however, have predominantly been conducted in Western societies. METHOD: Clinical diagnostic interviews and self-rated measures of psychological constructs, covering resilience, rumination, self-esteem and more, were administered to 860 youths aged 15 to 24 recruited from an ongoing epidemiological youth mental health study in Hong Kong. RESULTS: Three personality clusters were identified. The first (mean age = 19.6, 63.3% female) and second (mean age = 19.5, 60.7% female) cluster both have characteristics of the under- and overcontrolled personalities. The third personality type resembled the resilient profile in RUO typology (mean age = 19.6, 50.5% female) and showed the lowest prevalence of poor mental health. CONCLUSIONS: The results suggest that the replicability of the RUO profiles was only partial in a Hong Kong sample predominantly Chinese. The resilient profile was replicated but not the undercontrolled and overcontrolled profiles proposed by previous studies. The findings of the current study implicated that culturally contextual considerations are necessary when relating mental health to personality.

Effects of a culturally adapted counselling service for low-income ethnic minorities experiencing mental distress: a pragmatic randomised clinical trial.

BACKGROUND: Culturally competent early mental health interventions for ethnic minorities (EMs) with no formal diagnoses are needed. OBJECTIVES: To determine whether 8-12 weeks culturally adapted counselling (CAC) is better than waiting (waitlist (WL) group) to reduce depressive and anxiety symptoms and stress levels among EMs with elevated mental distress. METHODS: Hong Kong EMs with mild and above-mild mental distress were randomly assigned to CAC or WL in this pragmatic, randomised, WL-controlled trial. The CAC group received the intervention after randomisation and the WL group received the intervention after 8-12 weeks (T1). The prespecified primary outcomes were depressive and anxiety symptoms and stress levels measured by the Depression, Anxiety and Stress subscales of the Depression, Anxiety and Stress Scale (DASS-D, DASS-A and DASS-S, respectively) at postintervention (T1, 8-12 weeks). FINDINGS: A total of 120 participants were randomly assigned to either CAC (n=60) or WL (n=60), of whom 110 provided primary outcome data. At T1, CAC led to significantly lower depressive and anxiety symptom severity and stress levels compared with waiting, with unstandardised regression coefficients of -8.91 DASS-D points (95% CI -12.57 to -5.25; d=-0.90),-6.33 DASS-A points (95% CI -9.81 to -2.86; d=-0.68) and -8.60 DASS-S points (95% CI -12.14 to -5.06; d=-0.90). CONCLUSIONS: CAC clinically outperformed WL for mild and above-mild levels of mental distress in EMs. CLINICAL IMPLICATIONS: Making CAC routinely available for EMs in community settings can reduce healthcare burden. TRIAL REGISTRATION NUMBER: NCT04811170.

Unveiling common psychological characteristics of proneness to aggression and general psychopathology in a large community youth cohort.

Elevated aggression in individuals with psychiatric disorders is frequently reported yet aggressive acts among people with mental illness are often intertwined with proneness to aggression and other risk factors. Evidence has suggested that both general psychopathology and proneness to aggression may share common psychological characteristics. This study aims to investigate the complex relationship between general psychopathology, proneness to aggression, and their contributing factors in community youth. Here, we first examined the association between proneness to aggression and the level of general psychopathology in 2184 community youths (male: 41.2%). To identify common characteristics, we trained machine learning models using LASSO based on 230 features covering sociodemographic, cognitive functions, lifestyle, well-being, and psychological characteristics to predict levels of general psychopathology and proneness to aggression. A subsequent Gaussian Graph Model (GGM) was fitted to understand the relationships between the general psychopathology, proneness to aggression, and selected features. We showed that proneness to aggression was associated with a higher level of general psychopathology (discovery: r = 0.56, 95% CI: [0.52-0.59]; holdout: r = 0.60, 95% CI: [0.54-0.65]). The LASSO model trained on the discovery dataset for general psychopathology was able to predict proneness to aggression in the holdout dataset with a moderate correlation coefficient of 0.606. Similarly, the model trained on the proneness to aggression in the discovery dataset was able to predict general psychopathology in the holdout dataset with a correlation coefficient of 0.717. These results suggest that there is substantial shared information between the two outcomes. The GGM model revealed that isolation and impulsivity factors were directly associated with both general psychopathology and proneness to aggression. These results revealed shared psychological characteristics of general psychopathology and proneness to aggression in a community sample of youths.

Impact of early negative symptom patterns on the long-term outcomes of patients with first-episode schizophrenia-spectrum disorders: A 12-year follow up study.

Given the strong prognostic value of early negative symptoms (NS), understanding their associations with long-term outcomes of schizophrenia is essential. The study examined early NS patterns in trajectory, severity and variability and their association with 12-year outcomes. NS in the first 36 months after onset and the symptomatology, cognitive function, and functioning at 12 years were examined in 330 patients with first-episode schizophrenia spectrum disorders. The relationships and pathways between the outcomes at 12 years and the trajectory, severity, and variability of early NS were examined. We found that the prediction of trajectory of early NS to long-term outcomes was limited, whereas variability was negatively associated with the patient's long-term executive function, and severity was positively associated with long-term symptomatology and negatively associated with long-term functioning. Path modelling revealed that the severity and variability of early NS influenced patients' long-term functioning via cognitive function and/or clinical symptom pathways. Our findings support the notion that severity of early NS influences the prognosis of schizophrenia and the closer examination revealed that the severity and variability of early NS are differentially associated with long-term clinical symptoms, executive function, and functional outcomes via distinct pathways.

Impact of smartphone overuse on 1-year severe depressive symptoms and momentary negative affect: Longitudinal and experience sampling findings from a representative epidemiological youth sample in Hong Kong.

Smartphone overuse can have detrimental impacts on youth mental health. How it may be longitudinally associated with depressive symptoms and functioning, and with daily momentary affect, remains to be investigated. A total of 3,033 young people were consecutively recruited from a large-scale epidemiological youth mental health study in Hong Kong. A subsample (n = 936) was followed-up after 1 year, with experience sampling data collected from 177 participants. Separate multivariable logistic regression models were applied to examine the prospective associations between smartphone overuse and depressive symptoms, with multilevel models fitted to examine its associations with momentary affect. The prevalence of smartphone overuse in the Hong Kong youth population was 29.3%. Smartphone overuse was significantly associated with more depressive symptoms and functional impairments both cross-sectionally and longitudinally. The associations between smartphone overuse and 1-year depressive symptoms were significant, even when accounting for baseline symptoms, social media use, and other risk and protective factors. Baseline depressive symptoms, in contrast, were not associated with 1-year smartphone overuse after adjusting for baseline smartphone overuse. Smartphone overuse was also significantly associated with higher levels of momentary negative affect, even when accounting for depressive symptoms. Strategies to mitigate the impact of smartphone overuse can have important long-term implications.

Discovering the structure and organization of a free Cantonese emotion-label word association graph to understand mental lexicons of emotions.

Emotions are not necessarily universal across different languages and cultures. Mental lexicons of emotions depend strongly on contextual factors, such as language and culture. The Chinese language has unique linguistic properties that are different from other languages. As a main variant of Chinese, Cantonese has some emotional expressions that are only used by Cantonese speakers. Previous work on Chinese emotional vocabularies focused primarily on Mandarin. However, little is known about Cantonese emotion vocabularies. This is important since both language variants might have distinct emotional expressions, despite sharing the same writing system. To explore the structure and organization of Cantonese-label emotion words, we selected 79 highly representative emotion cue words from an ongoing large-scale Cantonese word association study (SWOW-HK). We aimed to identify the categories of these emotion words and non-emotion words that related to emotion concepts. Hierarchical cluster analysis was used to generate word clusters and investigate the underlying emotion dimensions. As the cluster quality was low in hierarchical clustering, we further constructed an emotion graph using a network approach to explore how emotions are organized in the Cantonese mental lexicon. With the support of emotion knowledge, the emotion graph defined more distinct emotion categories. The identified network communities covered basic emotions such as love, happiness, and sadness. Our results demonstrate that mental lexicon graphs constructed from free associations of Cantonese emotion-label words can reveal fine categories of emotions and their relevant concepts.

The role of education level on changes in endorsement of medication treatment and perceived public stigma towards psychosis in Hong Kong: comparison of three population-based surveys between 2009 and 2018.

OBJECTIVE: This study aimed to investigate the changes in perceived public stigma (PPS) towards psychosis, and endorsement of medication treatment between 2009 to 2018 in the Hong Kong Chinese population.The role of education level on the changes in PPS and endorsement of medication treatment for psychosis was also examined. METHODS: Telephone survey of the general population was conducted in 2009, 2014, and 2018. PPS was assessed using the revised Link's Perceived Discrimination-Devaluation Scale. Endorsement of medication was measured using an item asking if individuals with psychosis requires medication to manage their symptoms. Education level was separated into three categories (primary, secondary, and tertiary) for analysis. Factorial analysis of covariance was used to examine the main effects of survey year, education and endorsement of medication on stigma, and the interaction between survey year and education level, and survey year and endorsement of medication on PPS. RESULTS: 1016, 1018, and 1514 respondents completed the surveys in 2009, 2014, and 2018, respectively. PPS was found to be stable across the three public surveys. Endorsement of medication treatment was associated with higher PPS. An interaction effect between survey year and education level onPPS was observed. PPS was significantly lower and fewer respondents endorsed medication treatment in 2018 in the tertiary education group than in previous years. CONCLUSION: Current findings suggest that a targeted approach may be required for different education groups when developing anti-stigma public campaigns. Inclusion of other aspects of knowledge about psychosis may also be useful in reduction of PPS.

Dynamic Patterns of Symptoms and Functioning in Predicting Deliberate Self-harm in Patients with First-Episode Schizophrenia-Spectrum Disorders Over 3 Years.

OBJECTIVES: Patients with schizophrenia have a significant risk of self-harm. We aimed to explore the dynamic relationship between symptomatology, functioning and deliberate self-harm (DSH) and evaluate the feasibility of developing a self-harm risk prediction tool for patients with first-episode schizophrenia (FES). METHODS: Patients with FES (n = 1234) were followed up for 36 months. Symptomatology, functioning, treatment adherence and self-harm information were obtained monthly over the follow-up period. A time-varying vector autoregressive (VAR) model was used to study the contribution of clinical variables to self-harm over the 36th month. Random forest models for self-harm were established to classify the individuals with self-harm and predict future self-harm events. RESULTS: Over a 36-month period, 187 patients with FES had one or more self-harm events. The depressive symptoms contributed the most to self-harm prediction during the first year, while the importance of positive psychotic symptoms increased from the second year onwards. The random forest model with all static information and symptom instability achieved a good area under the receiver operating characteristic curve (AUROC = 0.77 ± 0.023) for identifying patients with DSH. With a sliding window analysis, the averaged AUROC of predicting a self-event was 0.65 ± 0.102 (ranging from 0.54 to 0.78) with the best model being 6-month predicted future 6-month self-harm for month 11-23 (AUROC = 0.7). CONCLUSIONS: Results highlight the importance of the dynamic relationship of depressive and positive psychotic symptoms with self-harm and the possibility of self-harm prediction in FES with longitudinal clinical data.

Impact of restrictive COVID-19 measures on daily momentary affect in an epidemiological youth sample in Hong Kong: An experience sampling study.

Restrictive COVID-19 measures can have significant mental health impacts, particularly on young people. How such measures may influence day-to-day momentary affect, nonetheless, remains to be explored. Experience sampling data were collected from 165 young people (aged 15-24) as part of a larger epidemiological youth mental health study in Hong Kong. We examined the impact of one of the most stringent COVID-19 measures - dine-in restrictions - on momentary positive and negative affect and current contexts and activities of these young people. The effects of a milder form of COVID-19 measure - school suspension - were separately examined. Multilevel analysis revealed that those in the dine-in ban group, compared to dining-as-usual, showed significantly reduced momentary positive affect (ß = -0.17, SE = 0.06, p = 0.003). Its effect remained significant even when accounting for baseline depressive and anxiety symptoms and socioeconomic status (ß = -0.15, SE = 0.05, p = 0.008). The effect of dine-in ban on reduced momentary positive affect was found specifically when participants were in indoor locations (e.g., home, office), alone, and engaged in passive leisure activities. This pattern was not observed when participants were at school or at other outdoor locations, with friends, or engaged in active leisure activities. No significant effect of school suspension on momentary affect was observed. More severe COVID-19 measures, such as dine-in ban, can have significant impacts on the momentary positive affect of young people. Certain contexts and activities may offer protection against the consequences of COVID-19 measures. The current findings may help to inform future designs of mental health interventions and public health policies. Supplementary Information: The online version contains supplementary material available at 10.1007/s12144-022-03183-y.

Gray Matter Abnormalities in Type 1 and Type 2 Diabetes: A Dual Disorder ALE Quantification.

Aims/hypothesis: Diabetes mellitus (DM) is associated with comorbid brain disorders. Neuroimaging studies in DM revealed neuronal degeneration in several cortical and subcortical brain regions. Previous studies indicate more pronounced brain alterations in type 2 diabetes mellitus (T2DM) than in type 1 diabetes mellitus (T1DM). However, a comparison of both types of DM in a single analysis has not been done so far. The aim of this meta-analysis was to conduct an unbiased objective investigation of neuroanatomical differences in DM by combining voxel-based morphometry (VBM) studies of T1DM and T2DM using dual disorder anatomical likelihood estimation (ALE) quantification. Methods: PubMed, Web of Science and Medline were systematically searched for publications until June 15, 2020. VBM studies comparing gray matter volume (GMV) differences between DM patients and controls at the whole-brain level were included. Study coordinates were entered into the ALE meta-analysis to investigate the extent to which T1DM, T2DM, or both conditions contribute to gray matter volume differences compared to controls. Results: Twenty studies (comprising of 1,175 patients matched with 1,013 controls) were included, with seven studies on GMV alterations in T1DM and 13 studies on GMV alterations in T2DM. ALE analysis revealed seven clusters of significantly lower GMV in T1DM and T2DM patients relative to controls across studies. Both DM subtypes showed GMV reductions in the left caudate, right superior temporal lobe, and left cuneus. Conversely, GMV reductions associated exclusively with T2DM (>99% contribution) were found in the left cingulate, right posterior lobe, right caudate and left occipital lobe. Meta-regression revealed no significant influence of study size, disease duration, and HbA1c values. Conclusions/interpretation: Our findings suggest a more pronounced gray matter atrophy in T2DM compared to T1DM. The increased risk of microvascular or macrovascular complications, as well as the disease-specific pathology of T2DM may contribute to observed GMV reductions. Systematic Review Registration: [PROSPERO], identifier [CRD42020142525].

Relationship between stressful life events, stigma and life satisfaction with the willingness of disclosure of psychotic illness: A community study in Hong Kong.

AIM: The preference of and potential barriers to disclosure of psychotic illness vary across cultures. Studying its patterns and correlates can guide the design of future culture-specific intervention and public education approaches to improve willingness to disclose and thereby reducing the duration of untreated psychosis (DUP). METHODS: A population-based, random telephone survey was conducted with a total of 1514 respondents in Hong Kong in January 2018. Cross-sectional data on willingness to disclose psychotic illness, life satisfaction, stigmatizing attitude and recent experience of stressful life events (SLEs) were analysed against age and gender using structural equation modelling (SEM). RESULTS: Unwillingness to disclose to anyone was reported by 12% of the participants. Family was reported as the preferred disclosure candidate by most respondents. Our model, which showed a good fit to the data demonstrated that stigmatizing attitude and life satisfaction were directly associated with willingness to disclose illness. Younger age was correlated with more recent experience of SLEs, lower life satisfaction and less willingness to disclose illness. Women's disclosure willingness was positively associated with their life satisfaction, which was sensitive to recent exposure to single SLE. In contrast, men's was negatively associated with their stigmatizing attitude, which increased significantly upon exposure to two or more recent SLEs. CONCLUSION: Encouraging the public to help their family to seek treatment should be a focal point of a successful mental health public education campaign. Cultural-specific and integrated interventions should be developed targeting the vulnerable groups including people with high recent life stress, particularly woman and those with younger age.

A single low dose of valproic acid in late prenatal life alters postnatal behavior and glutamic acid decarboxylase levels in the mouse.

RATIONALE: Rodents exposed to valproic acid (VPA) in prenatal life exhibit post-natal characteristics analogous to autism spectrum disorder (ASD). Many previous studies used relatively high doses of VPA during early pregnancy, potentially confounding interpretation because the offspring are the 'survivors' of a toxic insult. Low dose or late gestation exposure has not been widely studied. OBJECTIVES: We examined the behavioral sequelae of late gestation exposure to low dose VPA in the mouse. We also examined postnatal levels of glutamic acid decarboxylase (GAD65 and GAD67) as markers for GABA neurons, because GABA pathology and subsequent excitatory/inhibitory imbalance is strongly implicated in ASD. METHODS: Pregnant C57BL/6N mice received a single subcutaneous injection of 100 or 200mg/kg on gestation day 17. The control group received a saline injection on the same day. The offspring were tested in a battery of behavioral tests in adolescence and adulthood. Six brain regions were harvested and GAD65 and GAD67 were measured by western blotting. RESULTS: Compared to saline-exposed controls, adult mice exposed to prenatal VPA had impaired novel object exploration and fear conditioning anomalies. GAD67 was decreased in midbrain, olfactory bulb, prefrontal cortex and increased in cerebellum, hippocampus and striatum; GAD65 was decreased in all 6 regions. CONCLUSIONS: Our results suggest that a low dose of VPA in late pregnancy has persistent effects on brain development, and in particular the GABA system, which may be relevant to ASD. Further attention to the impact of gestation time and dose of exposure in VPA-induced ASD models is encouraged.

Tspyl2 Loss-of-Function Causes Neurodevelopmental Brain and Behavior Abnormalities in Mice.

Testis specific protein, Y-encoded-like 2 (TSPYL2) regulates the expression of genes encoding glutamate receptors. Glutamate pathology is implicated in neurodevelopmental conditions such as autism spectrum disorder, attention deficit hyperactivity disorder (ADHD) and schizophrenia. In line with this, a microduplication incorporating the TSPYL2 locus has been reported in people with ADHD. However, the role of Tspyl2 remains unclear. Therefore here we used a Tspyl2 loss-of-function mouse model to directly examine how this gene impacts upon behavior and brain anatomy. We hypothesized that Tspyl2 knockout (KO) would precipitate a phenotype relevant to neurodevelopmental conditions. In line with this prediction, we found that Tspyl2 KO mice were marginally more active, had significantly impaired prepulse inhibition, and were significantly more 'sensitive' to the dopamine agonist amphetamine. In addition, the lateral ventricles were significantly smaller in KO mice. These findings suggest that disrupting Tspyl2 gene expression leads to behavioral and brain morphological alterations that mirror a number of neurodevelopmental psychiatric traits.

Multimodal MRI of the hippocampus in Parkinson's disease with visual hallucinations.

Visual hallucinations carry poor prognosis in Parkinson's disease. Here we tested the hypothesis that the hippocampus and visuospatial memory impairment play a central role in the pathology of PD with visual hallucinations. Multimodal magnetic resonance imaging of the brain was carried out in 12 people with PD and visual hallucinations; 15 PD individuals without hallucinations; and 14 healthy controls. Age, gender, cognitive ability, and education level were matched across the three groups. PD patients were taking dopaminergic medication. Hippocampal volume, shape, mean diffusivity (MD), and functional connectivity within the whole brain were examined. Visuospatial memory was compared between groups, and correlations with hippocampal MD, functional connectivity, and the severity of hallucinations were explored. There were no macrostructural differences across groups, but individuals with hallucinations had higher diffusivity in posterior hippocampus than the other two groups. Visuospatial memory was poorer in both PD groups compared to controls, and was correlated with hallucinations. Finally, hippocampal functional connectivity in the visual cortices was lower in those with hallucinations than other groups, and this correlated with visuospatial memory impairment. In contrast, functional connectivity between the hippocampus and default mode network regions and frontal regions was greater in the PD hallucinators compared to other groups. We suggest that hippocampal pathology, which disrupts visuospatial memory, makes a key contribution to visual hallucinations in PD. These findings may pave the way for future studies of imaging biomarkers to measure treatment response in those with PD who are most at risk of poor outcomes.

Resting activity in visual and corticostriatal pathways in Parkinson's disease with hallucinations.

BACKGROUND: Visual hallucinations are an important non-motor complication of Parkinson's disease (PD) and carry a negative prognosis. Their biological basis is uncertain, but may relate to the activity of resting state networks in brain. We therefore aimed to investigate functional activity of brain in patients with visual hallucinations (PDVH) in resting state compared to patients without hallucinations (PDnonVH) and a healthy control group (HC). METHODS: Resting state functional MRI was acquired and the primary analysis compared the amplitude of low-frequency fluctuations (ALFF) across groups. This informed a secondary analysis, in the PD groups only, comparing functional connectivity between a 'seed' region in the occipital lobe and the rest of the brain. RESULTS: Individuals with PDVH showed lower ALFF in bilateral lingual gyrus and cuneus and greater ALFF in temporo-parietal regions, medial temporal gyrus and cerebellum than PDnonVH and HC. PDnonVH also had lower ALFF in occipitoparietal region and greater ALFF in medial temporal gyrus, temporo-parietal and cerebellum regions than HC. Functional connectivity analysis revealed that, although both PD groups had lower occipital functional connectivity relative to the HC group, occipital - corticostriatal connectivity was significantly higher in those with PDVH compared with PDnonVH. CONCLUSION: Our study reveals widespread hemodynamic alterations in PD. However, within a functionally abnormal occipital lobe, those with PDVH have even lower ALFF than non-hallucinators, but have higher occipital functional connectivity with cortical-striatal regions. These findings suggest disruption of pathways underpinning both primary visual perceptual and intrinsic visual integration may contribute to visual hallucinations in PD.

MRI predicts remission at 1 year in first-episode schizophrenia in females with larger striato-thalamic volumes.

BACKGROUND/AIMS: The Remission in Schizophrenia Working Group has defined remission as 'a low-mild symptom intensity level, maintained for a minimum of 6 months, where such symptoms do not affect an individual's behaviour' [Andreasen et al.: Am J Psychiatry 2005;162:441-449]. Since brain morphology relates to symptomatology, treatment and illness progression, MRI may assist in predicting remission. METHODS: Thirty-nine patients newly diagnosed with DSM-IV schizophrenia underwent MRI brain scan prior to antipsychotic exposure. The Global Assessment of Functioning (GAF) score was entered into a voxel-based analysis to evaluate its relationship with cerebral grey matter volume from the baseline MRI. We entered age, total intracranial volume and intake GAF score as co-variates. Males and females were analysed separately because gender is a potent determinant of outcome. RESULTS: Males had lower GAF scores than females, both at intake and at 1 year. Males comprised only 40% (12 out of 39) of the early remission group. For females only, early remission was strongly and positively correlated with bilateral lentiform and striatal volumes. For males, there was no such relationship. CONCLUSION: Larger striato-thalamic volume correlated with early remission in females only. These baseline MRI findings were unlikely to be confounded by antipsychotic treatment and chronicity. These brain morphological markers show gender dimorphism and may assist in the prediction of early remission in newly diagnosed schizophrenia.

The default mode network is disrupted in Parkinson's disease with visual hallucinations.

BACKGROUND: Visual hallucinations (VH) are one of the most striking nonmotor symptoms in Parkinson's disease (PD), and predict dementia and mortality. Aberrant default mode network (DMN) is associated with other psychoses. Here, we tested the hypothesis that DMN dysfunction contributes to VH in PD. METHODS: Resting state functional data was acquired from individuals with PD with VH (PDVH) and without VH (PDnonVH), matched for levodopa drug equivalent dose, and a healthy control group (HC). Independent component analysis was used to investigate group differences in functional connectivity within the DMN. In addition, we investigated whether the functional changes associated with hallucinations were accompanied by differences in cortical thickness. RESULTS: There were no group differences in cortical thickness but functional coactivation within components of the DMN was significantly lower in both PDVH and PDnonVH groups compared to HC. Functional coactivation within the DMN was found to be greater in PDVH group relative to PDnonVH group. CONCLUSION: Our study demonstrates, for the first time that, within a functionally abnormal DMN in PD, relatively higher "connectivity" is associated with VH. We postulate that aberrant connectivity in a large scale network affects sensory information processing and perception, and contributes to "positive" symptom generation in PD.

MRI study of minor physical anomaly in childhood autism implicates aberrant neurodevelopment in infancy.

BACKGROUND: MPAs (minor physical anomalies) frequently occur in neurodevelopmental disorders because both face and brain are derived from neuroectoderm in the first trimester. Conventionally, MPAs are measured by evaluation of external appearance. Using MRI can help overcome inherent observer bias, facilitate multi-centre data acquisition, and explore how MPAs relate to brain dysmorphology in the same individual. Optical MPAs exhibit a tightly synchronized trajectory through fetal, postnatal and adult life. As head size enlarges with age, inter-orbital distance increases, and is mostly completed before age 3 years. We hypothesized that optical MPAs might afford a retrospective 'window' to early neurodevelopment; specifically, inter-orbital distance increase may represent a biomarker for early brain dysmaturation in autism. METHODS: We recruited 91 children aged 7-16; 36 with an autism spectrum disorder and 55 age- and gender-matched typically developing controls. All children had normal IQ. Inter-orbital distance was measured on T1-weighted MRI scans. This value was entered into a voxel-by-voxel linear regression analysis with grey matter segmented from a bimodal MRI data-set. Age and total brain tissue volume were entered as covariates. RESULTS: Intra-class coefficient for measurement of the inter-orbital distance was 0.95. Inter-orbital distance was significantly increased in the autism group (p = 0.03, 2-tailed). The autism group showed a significant relationship between inter-orbital distance grey matter volume of bilateral amygdalae extending to the unci and inferior temporal poles. CONCLUSIONS: Greater inter-orbital distance in the autism group compared with healthy controls is consistent with infant head size expansion in autism. Inter-orbital distance positively correlated with volume of medial temporal lobe structures, suggesting a link to "social brain" dysmorphology in the autism group. We suggest these data support the role of optical MPAs as a "fossil record" of early aberrant neurodevelopment, and potential biomarker for brain dysmaturation in autism.

Possible retrogenesis observed with fiber tracking: an anteroposterior pattern of white matter disintegrity in normal aging and Alzheimer's disease.

Retrogenesis refers to the phenomenon by which degenerative processes in aging reverse the sequence of acquisition in development. Although there has been some evidence for brain retrogenesis in abnormal aging, e.g., Alzheimer's disease (AD), it has not been explicitly addressed in the normal aging. Using diffusion tensor imaging and tractography, we explored the effects of normal and abnormal aging on the integrity of white matter (WM) in fifty participants, including 18 AD patients, 17 normal elderly, and 15 normal young adults. Compared with young adults, the traditional voxel-based analysis, and the quantitative fiber tracking methods revealed lower fractional anisotrophy (FA) for both normal elderly and AD patients, indicating WM disintegrity in the anterior part of the brain with developmentally late-myelinating fiber bundles. Furthermore, AD patients showed lower FA in the posterior part of the brain with relatively early-myelinating fiber bundles. Additional analysis on axial diffusion and radial diffusion measures suggest that demyelination may be the main mechanism underlying the observed microstructural impairments. Consistent with a proposal of retrogenesis, our results demonstrate an anteroposterior pattern of white matter disintegrity in both normal aging and AD, with the pattern being more salient in the latter than in the former.

Can Asperger syndrome be distinguished from autism? An anatomic likelihood meta-analysis of MRI studies.

BACKGROUND: The question of whether Asperger syndrome can be distinguished from autism has attracted much debate and may even incur delay in diagnosis and intervention. Accordingly, there has been a proposal for Asperger syndrome to be subsumed under autism in the forthcoming Diagnostic and Statistical Manual of Mental Disorders, fifth edition, in 2013. One approach to resolve this question has been to adopt the criterion of absence of clinically significant language or cognitive delay--essentially, the "absence of language delay." To our knowledge, this is the first meta-analysis of magnetic resonance imaging (MRI) studies of people with autism to compare absence with presence of language delay. It capitalizes on the voxel-based morphometry (VBM) approach to systematically explore the whole brain for anatomic correlates of delay and no delay in language acquisition in people with autism spectrum disorders. METHODS: We conducted a systematic search for VBM MRI studies of grey matter volume in people with autism. Studies with a majority (at least 70%) of participants with autism diagnoses and a history of language delay were assigned to the autism group (n = 151, control n = 190). Those with a majority (at least 70%) of individuals with autism diagnoses and no language delay were assigned to the Asperger syndrome group (n = 149, control n = 214). We entered study coordinates into anatomic likelihood estimation meta-analysis software with sampling size weighting to compare grey matter summary maps driven by Asperger syndrome or autism. RESULTS: The summary autism grey matter map showed lower volumes in the cerebellum, right uncus, dorsal hippocampus and middle temporal gyrus compared with controls; grey matter volumes were greater in the bilateral caudate, prefrontal lobe and ventral temporal lobe. The summary Asperger syndrome map indicated lower grey matter volumes in the bilateral amygdala/hippocampal gyrus and prefrontal lobe, left occipital gyrus, right cerebellum, putamen and precuneus compared with controls; grey matter volumes were greater in more limited regions, including the bilateral inferior parietal lobule and the left fusiform gyrus. Both Asperger syndrome and autism studies reported volume increase in clusters in the ventral temporal lobe of the left hemisphere. LIMITATIONS: We assigned studies to autism and Asperger syndrome groups for separate analyses of the data and did not carry out a direct statistical group comparison. In addition, studies available for analysis did not capture the entire spectrum, therefore we cannot be certain that our findings apply to a wider population than that sampled. CONCLUSION: Whereas grey matter differences in people with Asperger syndrome compared with controls are sparser than those reported in studies of people with autism, the distribution and direction of differences in each category are distinctive.