Reduced cortical thickness in subjects at clinical high risk for psychosis and clinical attributes

Objectives: Although neuroanatomical abnormalities in subjects at clinical high risk for psychosis have been considered a putative biomarker of psychosis, relevance of cortical thickness alterations remains contested due to discrepant findings. Inconsistencies persist in Asian clinical high risk studies, despite their advantageous settings well-controlled for confounds. Attributes of cortical thickness alterations in clinical high risk subjects warrant further examination. Methods: We examined cortical thickness at the whole-brain level in 74 clinical high risk subjects and 34 demographically matched healthy controls recruited from Seoul Youth Clinic, South Korea. Clinical symptoms were assessed using the Scale of Prodromal Symptoms, and their associations with cortical thickness were explored using partial correlation analysis. Results: Compared to healthy control, clinical high risk exhibited significant cortical thinning in bilateral prefrontal cortex and inferior parietal lobule clusters. Reduced thickness in the left prefrontal cortex cluster was associated with more severe Scale of Prodromal Symptoms general symptoms scores and the right inferior parietal lobule cluster with Scale of Prodromal Symptoms disorganization symptoms. Conclusions: Thickness deficits found in the present clinical high risk sample demonstrated a degree of consistency with those reported in the previous Seoul Youth Clinic study. While inconsistencies reported between the present and previous Seoul Youth Clinic samples may reflect markedly decreased rate of converters, consistencies may be relevant to clinical attributes beyond transition, such as the prevalence of comorbidities. Particular recruitment strategies employed for sample selections should also be considered for findings in Asian clinical high risk samples. Our results suggest potential utility of cortical thickness alterations in clinical high risk subjects beyond the frame of transition.

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Changes in Brain Structure, Function, and Network Properties in Patients With First-Episode Schizophrenia Treated With Antipsychotics

Frontiers in Psychiatry ◽

10.3389/fpsyt.2021.735623 ◽

2021 ◽

Vol 12 ◽

Author(s):

Ping Yin ◽

Chao Zhao ◽

Yang Li ◽

Xiaoyi Liu ◽

Lei Chen ◽

...

Keyword(s):

Structure Function ◽

Clinical Symptoms ◽

First Episode ◽

Antipsychotic Treatment ◽

Precentral Gyrus ◽

Inferior Parietal Lobule ◽

Network Properties ◽

Parietal Lobule ◽

The Right ◽

First Episode Schizophrenia

Purpose: Comprehensive and longitudinal brain analysis is of great significance for understanding the pathological changes of antipsychotic drug treatment in patients with schizophrenia. This study aimed to investigate the changes of structure, function, and network properties in patients with first-episode schizophrenia (FES) after antipsychotic therapy and their relationship with clinical symptoms.Materials and Methods: A total of 30 patients diagnosed with FES and 30 healthy subjects matched for sex and age were enrolled in our study. Patients at baseline were labeled as antipsychotic-naive first-episode schizophrenia (AN-FES), and patients after antipsychotic treatment were labeled as antipsychotic treatment first-episode schizophrenia (AT-FES). The severity of illness was measured by using the PANSS and CGI score. Structural and functional MRI data were also performed. Differences in GMV, ALFF, and ReHo between the FES group and healthy control group were tested using a voxel-wise two-sample t-test, and the comparison of AN-FES group and AT-FES group was evaluated by paired-sample t-test.Results: After the 1-year follow-up, the FES patients showed increased GMV in the right cerebellum, right inferior temporal gyrus, left middle frontal gyrus, parahippocampal gyrus, bilateral inferior parietal lobule, and reduced GMV in the left occipital lobe, gyrus rectus, right orbital frontal cortex. The patients also showed increased ALFF in the medial superior frontal gyrus and right precentral gyrus. For network properties, the patients showed reduced characteristic path length and increased global efficiency. The GMV of the right inferior parietal lobule was negatively correlated with the clinical symptoms.Conclusions: Our study showed that the antipsychotic treatment contributed to the structural alteration and functional improvement, and the GMV alteration may be associated with the improvement of clinical symptoms.

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Dysregulation of complement and coagulation pathways: emerging mechanisms in the development of psychosis

Molecular Psychiatry ◽

10.1038/s41380-021-01197-9 ◽

2021 ◽

Author(s):

Meike Heurich ◽

Melanie Föcking ◽

David Mongan ◽

Gerard Cagney ◽

David R. Cotter

Keyword(s):

High Risk ◽

Psychotic Disorder ◽

Psychotic Disorders ◽

Clinical Symptoms ◽

First Episode Psychosis ◽

Specific Protein ◽

First Episode ◽

Clinical High Risk ◽

Blood Proteins ◽

Episode Psychosis

AbstractEarly identification and treatment significantly improve clinical outcomes of psychotic disorders. Recent studies identified protein components of the complement and coagulation systems as key pathways implicated in psychosis. These specific protein alterations are integral to the inflammatory response and can begin years before the onset of clinical symptoms of psychotic disorder. Critically, they have recently been shown to predict the transition from clinical high risk to first-episode psychosis, enabling stratification of individuals who are most likely to transition to psychotic disorder from those who are not. This reinforces the concept that the psychosis spectrum is likely a central nervous system manifestation of systemic changes and highlights the need to investigate plasma proteins as diagnostic or prognostic biomarkers and pathophysiological mediators. In this review, we integrate evidence of alterations in proteins belonging to the complement and coagulation protein systems, including the coagulation, anticoagulation, and fibrinolytic pathways and their dysregulation in psychosis, into a consolidated mechanism that could be integral to the progression and manifestation of psychosis. We consolidate the findings of altered blood proteins relevant for progression to psychotic disorders, using data from longitudinal studies of the general population in addition to clinical high-risk (CHR) individuals transitioning to psychotic disorder. These are compared to markers identified from first-episode psychosis and schizophrenia as well as other psychosis spectrum disorders. We propose the novel hypothesis that altered complement and coagulation plasma levels enhance their pathways’ activating capacities, while low levels observed in key regulatory components contribute to excessive activation observed in patients. This hypothesis will require future testing through a range of experimental paradigms, and if upheld, complement and coagulation pathways or specific proteins could be useful diagnostic or prognostic tools and targets for early intervention and preventive strategies.

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Effect of tDCS over the Right Inferior Parietal Lobule on Mind-Wandering Propensity

10.31234/osf.io/35thz ◽

2020 ◽

Author(s):

Sean Coulborn ◽

Howard Bowman ◽

Chris Miall ◽

Davinia Fernández-Espejo

Keyword(s):

Mind Wandering ◽

Inferior Parietal Lobule ◽

Double Blind ◽

Default Mode ◽

Dorsolateral Prefrontal ◽

Parietal Lobule ◽

Response Task ◽

Thought Probes ◽

The Right ◽

Subjective Reports

Mind-wandering is associated with switching our attention to internally directed thoughts and is by definition an intrinsic, self-generated cognitive function. Interestingly, previous research showed that it may be possible to modulate its propensity externally, with transcranial direct current stimulation (tDCS) targeting different regions in the default mode and executive control networks. However, these studies used highly heterogeneous montages (targeting the dorsolateral prefrontal cortex (DLPFC), the right inferior parietal lobule (IPL), or both concurrently), often showed contradicting results, and in many cases failed to replicate. Our study aimed to establish whether tDCS of the default mode network, via targeting the right IPL alone, could modulate mind-wandering propensity using a within-subjects double-blind, counterbalanced design. Participants completed a sustained attention to response task (SART) interspersed with thought-probes to capture their subjective reports of mind-wandering before and after receiving anodal, cathodal, or sham tDCS over the right IPL (with the reference over the left cheek). We found evidence for the lack of an effect of stimulation on subjective reports of mind-wandering (JZS-BF01 = 5.19), as well as on performance on the SART task (errors (JZS-BF01 = 6.79) and reaction time (JZS-BF01 = 5.94). Overall, we failed to replicate previous reports of successful modulations of mind-wandering propensity with tDCS over the IPL, instead providing evidence in support of the lack of an effect. This, and other recent unsuccessful replications call into question whether it is indeed possible to externally modulate spontaneous or self-generated cognitive processes.

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Influence of Atomoxetine on Relationship Between ADHD Symptoms and Prefrontal Cortex Activity During Task Execution in Adult Patients

Frontiers in Human Neuroscience ◽

10.3389/fnhum.2021.755025 ◽

2021 ◽

Vol 15 ◽

Author(s):

Atsunori Sugimoto ◽

Yutaro Suzuki ◽

Kiyohiro Yoshinaga ◽

Naoki Orime ◽

Taketsugu Hayashi ◽

...

Keyword(s):

Prefrontal Cortex ◽

Dorsolateral Prefrontal Cortex ◽

Rating Scales ◽

Clinical Symptoms ◽

Adult Patients ◽

Adhd Symptoms ◽

Analytical Strategy ◽

Positive Correlation ◽

Dorsolateral Prefrontal ◽

The Right

Objective: We conducted this non-randomized prospective interventional study to clarify the relationship between improved attention-deficit hyperactivity disorder (ADHD) symptoms and regional brain activity.Methods: Thirty-one adult patients underwent near-infrared spectroscopy examinations during a go/no-go task, both before and 8 weeks after atomoxetine administration.Results: Clinical symptoms, neuropsychological results of the go/no-go task, and bilateral lateral prefrontal activity significantly changed. A positive correlation was observed between right dorsolateral prefrontal cortex activity and Conners’ Adult ADHD Rating Scales scores. Before atomoxetine administration, no correlations between prefrontal cortex activity and clinical symptoms were observed in all cases. When participants were divided into atomoxetine-responder and non-responder groups, a positive correlation was observed between prefrontal cortex activity and clinical symptoms in the non-responder group before treatment but not in the responder group, suggesting that non-responders can activate the prefrontal cortex without atomoxetine.Conclusions: Individuals with increased ADHD symptoms appear to recruit the right dorsolateral prefrontal cortex more strongly to perform the same task than those with fewer symptoms. In clinical settings, individuals with severe symptoms are often observed to perform more difficultly when performing the tasks which individuals with mild symptoms can perform easily. The atomoxetine-responder group was unable to properly activate the right dorsolateral prefrontal cortex when necessary, and the oral administration of atomoxetine enabled these patients to activate this region. In brain imaging studies of heterogeneous syndromes such as ADHD, the analytical strategy used in this study, involving drug-responsivity grouping, may effectively increase the signal-to-noise ratio.

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Clinical subtypes that predict conversion to psychosis: A canonical correlation analysis study from the ShangHai At Risk for Psychosis program

Australian & New Zealand Journal of Psychiatry ◽

10.1177/0004867419872248 ◽

2019 ◽

Vol 54 (5) ◽

pp. 482-495 ◽

Cited By ~ 2

Author(s):

TianHong Zhang ◽

XiaoChen Tang ◽

HuiJun Li ◽

Kristen A Woodberry ◽

Emily R Kline ◽

...

Keyword(s):

At Risk ◽

Cluster Analysis ◽

High Risk ◽

Correlation Analysis ◽

Canonical Correlation Analysis ◽

Canonical Correlation ◽

Clinical Symptoms ◽

Structured Interview ◽

Two Dimensions ◽

Clinical High Risk

Objective: Since only 30% or fewer of individuals at clinical high risk convert to psychosis within 2 years, efforts are underway to refine risk identification strategies to increase their predictive power. The clinical high risk is a heterogeneous syndrome presenting with highly variable clinical symptoms and cognitive dysfunctions. This study investigated whether subtypes defined by baseline clinical and cognitive features improve the prediction of psychosis. Method: Four hundred clinical high-risk subjects from the ongoing ShangHai At Risk for Psychosis program were enrolled in a prospective cohort study. Canonical correlation analysis was applied to 289 clinical high-risk subjects with completed Structured Interview for Prodromal Syndromes and cognitive battery tests at baseline, and at least 1-year follow-up. Canonical variates were generated by canonical correlation analysis and then used for hierarchical cluster analysis to produce subtypes. Kaplan–Meier survival curves were constructed from the three subtypes to test their utility further in predicting psychosis. Results: Canonical correlation analysis determined two linear combinations: (1) negative symptom and functional deterioration-related cognitive features, and (2) Positive symptoms and emotional disorganization-related cognitive features. Cluster analysis revealed three subtypes defined by distinct and relatively homogeneous patterns along two dimensions, comprising 14.2% (subtype 1, n = 41), 37.4% (subtype 2, n = 108) and 48.4% (subtype 3, n = 140) of the sample, and each with distinctive features of clinical and cognitive performance. Those with subtype 1, which is characterized by extensive negative symptoms and cognitive deficits, appear to have the highest risk for psychosis. The conversion risk for subtypes 1–3 are 39.0%, 11.1% and 18.6%, respectively. Conclusion: Our results define important subtypes within clinical high-risk syndromes that highlight clinical symptoms and cognitive features that transcend current diagnostic boundaries. The three different subtypes reflect significant differences in clinical and cognitive characteristics as well as in the risk of conversion to psychosis.

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