Wanjun Guo

Hair Cortisol Level as a Biomarker for Altered Hypothalamic-Pituitary-Adrenal Activity in Female Adolescents with Posttraumatic Stress Disorder After the 2008 Wenchuan Earthquake

BACKGROUND The present study evaluated the accumulated changes in hair cortisol levels of patients with posttraumatic stress disorder (PTSD) attributed to the 2008 Wenchuan earthquake in China. METHODS Sixty-four female adolescents from two townships who experienced the earthquake were recruited 7 months after the disaster, including 32 subjects with PTSD (PTSD group) and 32 subjects without PTSD (non-PTSD group). Twenty matched adolescents were recruited from an area that was not affected significantly by the earthquake as the control group. Hair cortisol concentrations were measured by the electrochemiluminescence immunoassay in each 3-cm segment of hair sample from the scalp. RESULTS There was no significant difference at the baseline hair cortisol level in the three groups before the traumatic event (p > .6). Hair cortisol levels changed over time and differed among groups (p = .0042). The hair cortisol levels among the PTSD and non-PTSD subjects were elevated, suggesting increasing levels in response to stress. However, these two groups differed in their response. The non-PTSD subjects showed a significantly higher cortisol level than the PTSD group between month 2 and month 4 (p = .0137) and also between month 5 and month 7 (p = .0438) after the traumatic event. CONCLUSIONS This study revealed a blunted response curve to the disaster among PTSD subjects compared with subjects without PTSD. These findings suggest that hair cortisol level could be used to assess the integrated hypothalamic-pituitary-adrenal activity over a period of months after traumatic events and be used to serve as a biomarker in patients with PTSD.

The prefrontal dysfunction in individuals with Internet gaming disorder: a meta-analysis of functional magnetic resonance imaging studies.

With the advancement in high‐resolution magnetic resonance imaging (MRI) technology and automated analysis, studies on functional MRI (fMRI) made it possible to identify the functional activity of brain in vivo in individuals with Internet gaming disorder (IGD), and to explore the underpinning neuroscience basis of IGD. Yet, no available literature has systemically reviewed the fMRI studies of IGD using meta‐analyses. This study reviewed 61 candidate articles and finally selected 10 qualified voxel‐wise whole‐brain analysis studies for performing a comprehensive series of meta‐analyses employing effect size signed differential mapping approach. Compared with healthy controls, subjects with IGD showed a significant activation in the bilateral medial frontal gyrus (MFG) and the left cingulate gyrus, as well as the left medial temporal gyrus and fusiform gyrus. Furthermore, the on‐line time of IGD subjects was positively correlated with activations in the left MFG and the right cingulated gyrus. These findings implicate the important role of dysfunctional prefrontal lobe in the neuropathological mechanism of IGD. Considering the overlapped role of prefrontal lobe in the reward and self‐regulatory system, our results provided supportive evidence for the reclassification of IGD as a behavioural addiction.

Voxel-based, brain-wide association study of aberrant functional connectivity in schizophrenia implicates thalamocortical circuitry

Background:Wernicke’s concept of ‘sejunction’ or aberrant associations among specialized brain regions is one of the earliest hypotheses attempting to explain the myriad of symptoms in psychotic disorders. Unbiased data mining of all possible brain-wide connections in large data sets is an essential first step in localizing these aberrant circuits.Methods:We analyzed functional connectivity using the largest resting-state neuroimaging data set reported to date in the schizophrenia literature (415 patients vs. 405 controls from UK, USA, Taiwan, and China). An exhaustive brain-wide association study at both regional and voxel-based levels enabled a continuous data-driven discovery of the key aberrant circuits in schizophrenia.Results:Results identify the thalamus as the key hub for altered functional networks in patients. Increased thalamus–primary somatosensory cortex connectivity was the most significant aberration in schizophrenia (P=10−18). Overall, a number of thalamic links with motor and sensory cortical regions showed increased connectivity in schizophrenia, whereas thalamo–frontal connectivity was weakened. Network changes were correlated with symptom severity and illness duration, and support vector machine analysis revealed discrimination accuracies of 73.53–80.92%.Conclusions:Widespread alterations in resting-state thalamocortical functional connectivity is likely to be a core feature of schizophrenia that contributes to the extensive sensory, motor, cognitive, and emotional impairments in this disorder. Changes in this schizophrenia-associated network could be a reliable mechanistic index to discriminate patients from healthy controls.

Validating GWAS-Identified Risk Loci for Alzheimer's Disease in Han Chinese Populations

In recent years, genome-wide association studies (GWASs) have identified many novel susceptible genes/loci for Alzheimer’s disease (AD). However, most of these studies were conducted in European and populations of European origin, and limited studies have been performed in Han Chinese. In this study, we genotyped 14 single-nucleotide polymorphisms (SNPs) in eight GWAS-reported AD risk genes in 1509 individuals comprising two independent Han Chinese case-control cohorts. Four SNPs (rs11234495, rs592297, rs676733, and rs3851179) in the PICALM gene were significantly associated with late-onset (LO)-AD in populations from Southwest China, whereas SNPs rs744373 (BIN1), rs9331942 (CLU), and rs670139 (MS4A4E) were linked to LO-AD in populations from East China. In the combined Han Chinese population, positive associations were observed between PICALM, CLU, MS4A4E genes, and LO-AD. The association between rs3851179 (PICALM), rs744373 (BIN1), and AD was further confirmed by meta-analysis of Asian populations. Our study verified the association between PICALM, BIN1, CLU, and MS4A4E variants and AD susceptibility in Han Chinese populations. We also discerned some regional differences concerning AD susceptibility SNPs.

Overlapping clusters of gray matter deficits in paranoid schizophrenia and psychotic bipolar mania with family history

The purpose of this study was to assess volumetric abnormalities of gray matter throughout the entire brain in patients with paranoid schizophrenia or with bipolar mania compared with control groups. We obtained weighted 3D T1 magnetic resonance images from 23 patients with paranoid schizophrenia, 24 patients with psychotic bipolar mania, and 36 healthy controls. Gray matter volume differences were assessed using optimized volumetric voxel-based morphometry (VBM). Both paranoid schizophrenia and bipolar mania group showed reduction of gray matter volume in the superior temporal gyrus (STG) (Brodmann Area, BA 22 areas), and the inferior parietal lobule, and enlargement of putamen, although different sides of the inferior parietal lobule and putamen were affected in the groups. Our findings showed the presence of overlapping clusters of gray matter deficits in paranoid-type schizophrenia and psychotic bipolar mania. The overlap in gray matter pathology between the two disorders may be attributed to risk factors common to both disorders.

Reward pathway dysfunction in gambling disorder: A meta-analysis of functional magnetic resonance imaging studies.

Recent emerging functional magnetic resonance imaging (fMRI) studies have identified many brain regions in which gambling cues or rewards elicit activation and may shed light upon the ongoing disputes regarding the diagnostic and neuroscientific issues of gambling disorder (GD). However, no studies to date have systemically reviewed fMRI studies of GD to analyze the brain areas activated by gambling-related cues and examine whether these areas were differentially activated between cases and healthy controls (HC). This study reviewed 62 candidate articles and ultimately selected 13 qualified voxel-wise whole brain analysis studies to perform a comprehensive series of meta-analyses using the effect size-signed differential mapping approach. Compared with HC, GD patients showed significant activation in right lentiform nucleus and left middle occipital gyrus. The increased activities in the lentiform nucleus compared to HC were also found in both GD subgroups, regardless of excluding or not excluding any kind of substance use disorder. In addition, the South Oaks Gambling Screen scores were associated with hyperactivity in right lentiform nucleus and bilateral parahippocampus, but negatively related to right middle frontal gyrus. These results suggest dysfunction within the frontostriatal cortical pathway in GD, which could contribute to our understanding of the categories and definition of GD and provide evidence for the reclassification of GD as a behavioral addiction in the DSM-5.

Contrasting and convergent patterns of amygdala connectivity in mania and depression: a resting-state study.

BACKGROUND wMania and depression in bipolar disorder (BP) manifest two extremes of aberrant emotional, physiologic and behavioral arousal states despite similarities in treatment response and neurocognitive deficits. We used resting-state functional magnetic resonance imaging (rsfMRI) to explore the common and unique abnormal functional connectivity underlying acute manic or depressed state in BP. METHODS 18 Patients with bipolar mania (BM), 10 patients with bipolar depression (BD) and 28 healthy controls underwent resting-state functional magnetic resonance imaging scanning. Left and right amygdala seed-to-voxel based functional connectivity were assessed and compared among the three groups. The relationships between aberrant functional connectivity and the severity of clinical symptoms, number of episodes, illness duration were investigated. RESULTS Compared to healthy controls, both BM and BD groups showed reduced functional connectivity between bilateral amygdala and inferior frontal gyrus (orbital), striatum, right lingual gyrus and posterior cerebellar lobe. Furthermore right amygdala-hippocampal connectivity was decreased in BD but increased in BM. No significant correlations were found between strength of abnormal functional connectivity and clinical characteristic in BD or BM. LIMITATIONS No euthymic subjects were recruited, and the patients in current study were all on medication. CONCLUSIONS The presence of substantial overlap in the pattern of disturbed connectivity between amygdala and frontal, striatal, lingual and cerebellar regions suggests mood state-independent dysconnectivity. The contrasting pattern of functional connectivity between right amygdala and hippocampus in BD and BM provides a novel lead to the probable mechanistic differences in these two extremes of mood states.

White matter alterations in first episode treatment-naïve patients with deficit schizophrenia: a combined VBM and DTI study

Categorizing ‘deficit schizophrenia’ (DS) as distinct from ‘non-deficit’ schizophrenia (NDS) may help reduce heterogeneity within schizophrenia. However, it is unknown if DS has a discrete white matter signature. Here we used MRI to compare white matter volume (voxel-based morphometry) and microstructural integrity (fractional anisotropy, FA) in first-episode treatment-naïve patients with DS and NDS and their unaffected relatives to control groups of similar age. We found that white matter disruption was prominent in DS compared to controls; the DS group had lower volumes in the cerebellum, bilateral extra-nuclear and bilateral frontoparietal regions, and lower FA in the body of corpus callosum, posterior superior longitudinal fasciculus and uncinate fasciculus. The DS group also had lower volume in bilateral extra-nuclear regions compared to NDS, and the volume of these clusters was negatively correlated with deficit symptom ratings. NDS patients however, had no significant volume alterations and limited disruption of microstructural integrity compared to controls. Finally, first-degree relatives of those with DS shared volume abnormalities in right extra-nuclear white matter. Thus, white matter pathology in schizophrenia is most evident in the deficit condition, and lower extra-nuclear white matter volumes in both DS patients and their relatives may represent a brain structural ‘endophenotype’ for DS.

Sex-Specific Patterns of Aberrant Brain Function in First-Episode Treatment-Naive Patients with Schizophrenia

Male and female patients with schizophrenia show significant differences in a number of important clinical features, yet the neural substrates of these differences are still poorly understood. Here we explored the sex differences in the brain functional aberrations in 124 treatment-naïve patients with first-episode schizophrenia (61 males), compared with 102 age-matched healthy controls (50 males). Maps of degree centrality (DC) and amplitude of low-frequency fluctuations (ALFF) were constructed using resting-state functional magnetic resonance imaging data and compared between groups. We found that: (1) Selective DC reduction was observed in the right putamen (Put_R) in male patients and the left middle frontal gyrus (MFG) in female patients; (2) Functional connectivity analysis (using Put_R and MFG as seeds) found that male and female patients have disturbed functional integration in two separate networks, i.e., the sensorimotor network and the default mode network; (3) Significant ALFF alterations were also observed in these two networks in both genders; (4) Sex specific brain functional alterations were associated with various symptoms in patients. These results suggested that sex-specific patterns of functional aberration existed in schizophrenia, and these patterns were associated with the clinical features both in male and female patients.

Anti-N-methyl-d-aspartate receptor encephalitis in a patient with a 7-year history of being diagnosed as schizophrenia: complexities in diagnosis and treatment

Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is a form of autoimmune encephalitis associated with antibodies against the NR1 subunits of NMDARs. Although new-onset acute prominent psychotic syndromes in patients with NMDAR encephalitis have been well documented, there is a lack of case studies on differential diagnosis and treatment of anti-NMDAR encephalitis after a long-term diagnostic history of functional psychotic disorders. The present study reports an unusual case of anti-NMDAR encephalitis. The patient had been diagnosed with schizophrenia 7 years earlier, and was currently hospitalized for acute-onset psychiatric symptoms. The diagnosis became unclear when the initial psychosis was confounded with considerations of other neurotoxicities (such as neuroleptic malignant syndrome). Finally, identification of specific immunoglobulin G NR1 autoantibodies in the cerebrospinal fluid and greater effectiveness of immunotherapy over antipsychotics alone (which has been well documented in anti-NMDAR encephalitis) indicated the diagnosis of anti-NMDAR encephalitis in this case. Based on the available evidence, however, the relationship between the newly diagnosed anti-NMDAR encephalitis and the seemingly clear, long-term history of schizophrenia in the preceding 7 years is uncertain. This case report illustrates that psychiatrists should consider anti-NMDAR encephalitis and order tests for specific immunoglobulin G NR1 autoantibodies in patients presenting with disorientation, disturbance of consciousness, cognitive deficit, dyskinesia, autonomic disturbance, or rapid deterioration, even with a seemingly clear history of a psychiatric disorder and no specific findings on routine neuroimaging, electroencephalography, or cerebrospinal fluid tests in the early stage of the illness.