Search

Background: Relatives of individuals with bipolar disorder (BD) are at higher risk of developing the disorder. Identifying brain alterations associated with familial vulnerability in BD can help discover endophenotypes, which are quantifiable biological traits more prevalent in unaffected relatives of BD (BD-RELs) than the general population. This review aimed at expanding our knowledge on endophenotypes of BD by providing an overview of resting-state functional magnetic resonance imaging (rs-fMRI) alterations in BD-RELs., Methods: A systematic search of PubMed, Scopus, and Web of Science was performed to identify all available rs-fMRI studies conducted in BD-RELs up to January 2024. A total of 18 studies were selected. Six included BD-RELs with no history of psychiatric disorders and 10 included BD-RELs that presented psychiatric disorders. Two investigations examined rs-fMRI alterations in BD-RELs with and without subthreshold symptoms for BD., Results: BD-RELs presented rs-fMRI alterations in the cortico-limbic network, fronto-thalamic-striatal circuit, fronto-occipital network, and, to a lesser extent, in the default mode network. This was true both for BD-RELs with no history of psychopathology and for BD-RELs that presented psychiatric disorders. The direct comparison of rs-fMRI alterations in BD-RELs with and without psychiatric symptoms displayed largely non-overlapping patterns of rs-fMRI abnormalities., Limitations: Small sample sizes and the clinical heterogeneity of BD-RELs limit the generalizability of our findings., Conclusions: The current literature suggests that first-degree BD-RELs exhibit rs-fMRI alterations in brain circuits involved in emotion regulation, cognition, reward processing, and psychosis susceptibility. Future studies are needed to validate these findings and to explore their potential as biomarkers for early detection and intervention., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Major Depression Disorder (MDD) and pain appear to be reciprocal risk factors and sharing common neuroanatomical pathways and biological substrates. However, the role of MDD on pain processing remains still unclear. Therefore, this review aims to focus on the effect of depression on pain anticipation, and perception, before and after treatment, through functional magnetic resonance imaging (fMRI)., Methods: A bibliographic search was conducted on PubMed, Scopus and Web of Science, looking for fMRI studies exploring pain processing in MDD patients., Results: Amongst the 602 studies retrieved, 12 met the inclusion criteria. In terms of pain perception, studies evidenced that MDD patients generally presented increased activation in brain regions within the prefrontal cortex, insula and in the limbic system (such as amygdala, hippocampus) and occipital cortex. The studies investigating the effect of antidepressant treatment evidenced a reduced activation in areas such as insula, anterior cingulate, and prefrontal cortices. In terms of pain anticipation, contrasting results were evidenced in MDD patients, which presented both increased and decreased activity in the prefrontal cortex, the insula and the temporal lobe, alongside with increased activity in the anterior cingulate cortex, the frontal gyrus and occipital lobes., Limitations: The small number of included studies, the heterogeneous approaches of the studies might limit the conclusions of this review., Conclusions: Acute pain processing in MDD patients seems to involve numerous and different brain areas. However, more specific fMRI studies with a more homogeneous population and rigorous approach should be conducted to better highlight the effect of depression on pain processing., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Psychosis onset is a transdiagnostic event that leads to a range of psychiatric disorders, which are currently diagnosed through clinical observation. The integration of multimodal biological data could reveal different subtypes of psychosis onset to target for the personalization of care. In this study, we tested the existence of subgroups of patients affected by first-episode psychosis (FEP) with a possible immunopathogenic basis. To do this, we designed a data-driven unsupervised machine learning model to cluster a sample of 127 FEP patients and 117 healthy controls (HC), based on the peripheral blood expression levels of 12 psychosis-related immune gene transcripts. To validate the model, we applied a resampling strategy based on the half-splitting of the total sample with random allocation of the cases. Further, we performed a post-hoc univariate analysis to verify the clinical, cognitive, and structural brain correlates of the subgroups identified. The model identified and validated two distinct clusters: 1) a FEP cluster characterized by the high expression of inflammatory and immune-activating genes (IL1B, CCR7, IL12A and CXCR3); 2) a cluster consisting of an equal number of FEP and HC subjects, which did not show a relative over or under expression of any immune marker (balanced subgroup). None of the subgroups was related to specific symptoms dimensions or longitudinal diagnosis of affective vs non-affective psychosis. FEP patients included in the balanced immune subgroup showed a thinning of the left supramarginal and superiorfrontal cortex (FDR-adjusted p-values < 0.05). Our results demonstrated the existence of a FEP patients' subgroup identified by a multivariate pattern of immunomarkers involved in inflammatory activation. This evidence may pave the way to sample stratification in clinical studies aiming to develop diagnostic tools and therapies targeting specific immunopathogenic pathways of psychosis., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Schizophrenia is a debilitating neuropsychiatric disorder that affects approximately 1% of the population and poses a major public health problem. Despite over 100 years of study, the treatment for schizophrenia remains limited, partially due to the lack of knowledge about the neural mechanisms of the illness and how they relate to symptoms. The US Food and Drug Administration (FDA) and the National Institute of Health (NIH) have provided seven biomarker categories that indicate causes, risks, and treatment responses. However, no FDA-approved biomarkers exist for psychiatric conditions, including schizophrenia, highlighting the need for biomarker development. Over three decades, magnetic resonance imaging (MRI)-based studies have identified patterns of abnormal brain function in schizophrenia. By using functional connectivity (FC) data, which gauges how brain regions interact over time, these studies have differentiated patient subgroups, predicted responses to antipsychotic medication, and correlated neural changes with symptoms. This suggests FC metrics could serve as promising biomarkers. Here, we present a selective review of studies leveraging MRI-derived FC to study neural alterations in schizophrenia, discuss how they align with FDA-NIH biomarkers, and outline the challenges and goals for developing FC biomarkers in schizophrenia., (© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

According to classical phenomenology, phenomenal experience is composed of perceptions (related to environmental stimuli) and imagery/ideas (unrelated to environmental stimuli). Intensity/vividness is supposed to represent the key phenomenal difference between perceptions and ideas, higher in perceptions than ideas, and thus the core subjective criterion to distinguish reality from imagination. At a neural level, phenomenal experience is related to brain activity in the sensory areas, driven by receptor stimulation (underlying perception) or associative areas (underlying imagery/ideas). An alteration of the phenomenal experience that leads to a loss of contact with reality characterizes psychosis, which mainly consists of hallucinations (false perceptions) and delusions (fixed ideas). According to the current data on their neural correlates across subclinical conditions and different neuropsychiatric disorders (such as schizophrenia), hallucinations are mainly associated with: transient (modality-specific) activations of sensory cortices (primarily superior temporal gyrus, occipito-temporal cortex, postcentral gyrus, and insula) during the hallucinatory experience; increased intrinsic activity/connectivity of associative/default-mode network (DMN) areas (primarily temporoparietal junction, posterior cingulate cortex, and medial prefrontal cortex); and deficits in the sensory systems. Analogously, delusions are mainly associated with increased intrinsic activity/connectivity of associative/DMN areas (primarily medial prefrontal cortex). Integrating these data into our three-dimensional model of neural activity and phenomenal-behavioral patterns, we propose the following model of psychosis. A functional/structural deficit in the sensory systems complemented by a functional reconfiguration of intrinsic brain activity favoring hyperactivity of associative/DMN areas may drive neuronal activations in the sensory (auditory/visual/somatosensory) areas and insular (interoceptive) areas with spatiotemporal configurations maximally independent from environmental stimuli and predominantly related to associative processing. This manifests in perception deficit and imagery/ideas composed of exteroceptive-like and interoceptive/affective-like elements that show a phenomenal intensity indistinguishable from perceptions, impairing the reality monitoring, along with minimal changeability by environmental stimuli, ultimately resulting in dissociation of the phenomenal experience from the environment, i.e., psychosis., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Cannabis is the illicit drug most commonly used worldwide, and its consumption can both induce psychiatric symptoms in otherwise healthy subjects and unmask a florid psychotic picture in patients with a prior psychotic risk. Previous studies suggest that chronic and long-term cannabis exposure may exert significant negative effects in brain areas enriched with cannabinoid receptors. However, whether brain alterations determined by cannabis dependency will lead to a clinically significant phenotype or to a psychotic outbreak at some point of an abuser's life remains unclear. The aim of this study was to investigate morphological brain differences between chronic cannabis users with cannabis-induced psychosis (CIP) and non-psychotic cannabis users (NPCU) without any psychiatric conditions and correlate brain deficits with selective socio-demographic, clinical and psychosocial variables. 3T magnetic resonance imaging (MRI) scans of 10 CIP patients and 12 NPCU were acquired. The type of drug, the frequency, and the duration, as well socio-demographic, clinical and psychosocial parameters of dependency were measured. CIP patients had extensive grey matter (GM) decreases in right superior frontal gyrus, right precentral, right superior temporal gyrus, insula bilaterally, right precuneus, right medial occipital gyrus, right fusiform gyrus, and left hippocampus in comparison to chronic cannabis users without psychosis. Finally, in CIP patients, the results showed a negative correlation between a domain of the Brief Psychiatric Rating Scale (BPRS), BPRS-Activity, and selective GM volumes. Overall, the results suggest that cannabis-induced psychosis is characterized by selective brain reductions that are not present in NPCU. Therefore, neuroimaging studies may provide a potential ground for identifying putative biomarkers associated with the risk of developing psychosis in cannabis users.

Magnetic resonance imaging (MRI) studies have identified neural structures implicated in the pathophysiology of mood disorders, especially bipolar disorder (BD) and major depressive disorder (MDD). However, the role of genetic and environmental influences on such brain deficits is still unclear. In this context, the present review summarizes the current evidence from structural MRI and Diffusion Tensor Imaging (DTI) studies on twin samples concordant or discordant for BD or MDD, with the aim of clarifying the role of genetic and environmental risk factors on brain alterations. Although the results showed a complex interplay between gene and environment in affective disorders, the evidence seem to underline that both genetic and environmental risk factors have an impact on brain areas and vulnerability to MDD and BD. However, the precise mechanism of action and the interaction between these factors still needs to be unveiled. Therefore, future larger studies on concordant or discordant twins should be encouraged, because this population provides a unique opportunity to probe separately genetic and environmental markers of disease vulnerability., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Polycystic ovary syndrome (PCOS) is the most common feminine endocrine disorder, characterized by androgen excess, ovulatory dysfunction, and polycystic ovarian morphology. The negative impact of symptoms on the quality of life (QoL) of patients is still not clear., Purpose: The present review aimed at studying the impact of the symptoms, the psychological symptoms, and brain alterations in women with PCOS., Methods: A systematic search was undertaken for studies that assessed the impact of PCOS symptoms on QoL, psychological symptoms, and brain alterations in PCOS patients., Results: Most of the information about QoL came from psychometric studies, which used culture-based questionnaires. Alterations of sleep quality, body image, and mood disorders can negatively affect the QoL of the patients. Sexual satisfaction and desire were affected by PCOS. Brain imaging studies showed functional alterations that are associated with impairments of visuospatial working memory, episodic and verbal memory, attention, and executive function., Conclusions: Several factors can negatively influence the quality of life of the patients, and they are directly related to hyperandrogenism and the risk of infertility. In particular, obesity, hirsutism, acne, and the fear of infertility can have a direct impact on self-esteem and sexual function. Metabolic and psychiatric comorbidities, such as mood, anxiety, and eating disorders, can affect the well-being of the patients. Moreover, specific cognitive alterations, such as impairments in attention and memory, can limit PCOS patients in a series of aspects of daily life., (© 2024. The Author(s).)

Maternal obesity before or during pregnancy has been associated previously in offspring with a wide range of poor neurodevelopmental outcomes and mental health problems. The effects of maternal obesity on offspring brain structure and function that may be responsible for these poor outcomes are not well understood. We, therefore, undertook a systematic review of magnetic resonance imaging (MRI) studies that have assessed the associations of maternal obesity with brain measures in offspring. A systematic search was conducted in PubMed, Web of Science, Scopus, and PsycINFO on August 20, 2023. Of 15 eligible studies, seven employed functional MRI (fMRI), five diffusion tensor imaging (DTI), and four anatomical MRI (one used both DTI and anatomical MRI) in the offspring. The ages of offspring varied widely: one was a study of fetuses in utero, five of neonates, one of infants, five of school-aged children, two of both neonates and infants, and one of both children and adults. Collectively, 12 studies reported significant associations of maternal obesity with structural or functional alterations of the offspring's brain, most frequently in the prefrontal cortex and limbic system. In conclusion, maternal obesity appears to have a profound influence on offspring brain development, particularly within the prefrontal and limbic networks that regulate emotion and behavior. Further studies are needed to identify how changes in brain structure and function mediate the effects of maternal obesity on long-term emotional and behavioral outcomes, as well as the molecular pathways through which maternal obesity alters offspring brain development., (© 2024 The Author(s). Journal of Neuroscience Research published by Wiley Periodicals LLC.)

Objectives: Brain imaging studies carried out in patients suffering from generalized anxiety disorder (GAD) have contributed to better characterize the pathophysiological mechanisms underlying this disorder. The present study reviews the available functional and structural brain imaging evidence on GAD, and suggests further strategies for investigations in this field., Methods: A systematic literature review was performed in PubMed, PsycINFO, and Google Scholar, aiming to identify original research evaluating GAD patients with the use of structural and functional magnetic resonance imaging as well as diffusion tensor imaging., Results: The available studies have shown impairments in ventrolateral and dorsolateral prefrontal cortex, anterior cingulate, posterior parietal regions, and amygdala in both pediatric and adult GAD patients, mostly in the right hemisphere. However, the literature is often tentative, given that most studies have employed small samples and included patients with comorbidities or in current use of various medications. Finally, different methodological aspects, such as the type of imaging equipment used, also complicate the generalizability of the findings., Conclusions: Longitudinal neuroimaging studies with larger samples of both juvenile and adult GAD patients, as well as at risk individuals and unaffected relatives, should be carried out in order to shed light on the specific biological signature of GAD.

The subplate (SP) represents a transitory cytoarchitectural fetal compartment containing most subcortical and cortico-cortical afferents, and has a fundamental role in the structural development of the healthy adult brain. There is evidence that schizophrenia and autism may be determined by developmental defects in the cortex or cortical circuitry during the earliest stages of pregnancy. This article provides an overview on fetal SP development, considering its role in schizophrenia and autism, as supported by a systematic review of the main databases. The SP has been described as a cortical amplifier with a role in the coordination of cortical activity, and sensitive growth and migration windows have crucial consequences with respect to cognitive functioning. Although there are not enough studies to draw final conclusions, improved knowledge of the SP's role in schizophrenia and autism spectrum disorders may help to elucidate and possibly prevent the onset of these two severe disorders., (Copyright © 2019 IBRO. Published by Elsevier Ltd. All rights reserved.)

Background: Somatoform disorders (SDs) are a heterogeneous group of psychiatric syndromes characterized by common symptoms, which may mimic a physical condition but they are not explained by a medical condition. Although the biologic nature of this disorder has been widely accepted, the neuroanatomical correlates characterizing SDs are still inconclusive., Objective: This study aims to explore gray matter (GM) volume alterations in SD patients compared to healthy controls and their possible association with clinical and cognitive measures., Method: We used voxel-based morphometry to examine regional GM volumes in 20 inpatients with SDs and 24-matched healthy controls. Only for SD patients, we employed multiple instruments to assess psychopathology and cognitive functioning, which were then used to explore their association with GM volume deficits., Results: Compared to healthy controls, SD patients showed GM volume reductions in the hypothalamus, left fusiform gyrus, right cuneus, left inferior frontal gyrus, left posterior cingulate, and right amygdala (p < 0.05, cluster Family Wise Error corrected). Additionally, in SD, Symptom Checklist-90-Phobia and Hamilton Depressive Rating Scale scores negatively correlated with specific fronto-temporoparietal regions whereas Symptom Checklist-90-Sleep scores positively correlated with anterior cingulate cortex. Lastly, the Boston Naming Test negatively correlated with fronto-temporoparietal and striatal volumes whereas Free and Cued Selective Reminding Test and Stroop scores positively correlated with superior temporal gyrus and cuneus, respectively (all p < 0.05, cluster Family Wise Error corrected)., Conclusion: Our results suggest that SDs might be characterized by selective impairments in specific cortico-limbic regions associated to two overlapping circuits, the neuromatrix of pain and the emotion regulation system., (Copyright © 2018 Academy of Consultation-Liaison Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objective: Olanzapine is an atypical antipsychotic that is widely used in the treatment of schizophrenia and has shown some degree of efficacy on negative and cognitive symptoms. We aimed to review the effects of olanzapine treatment on brain regions that are directly involved in cognitive and emotional processing., Methods: We used the PubMed database to perform a bibliographic search on functional magnetic resonance imaging studies that investigated the effects of olanzapine treatment on neural activity in patients with schizophrenia during cognitive and emotional tasks., Results: Despite the high variability of tasks and analysis methods employed, the weight of the evidence was consistent with the hypothesis that olanzapine treatment is associated with a normalization of brain activity in schizophrenia. Distinctive functional changes were found in frontal cortex and cingulate cortex activity during both cognitive and emotional tasks. During emotional processing, olanzapine treatment seems to specifically regulate the activity of the striatum and limbic system., Conclusions: The results of the reviewed studies suggest that in patients with schizophrenia, olanzapine treatment might lead to a more physiological brain activity coupled with regulation of dopamine release. Future studies should further corroborate these hypotheses using larger samples and homogeneous experimental tasks., (© 2019 John Wiley & Sons, Ltd.)

Cognitive impairment is strongly associated with functional outcomes in psychiatric patients. Involvement of n -3 long chain polyunsaturated fatty acid ( n -3 LC-PUFA), in particular docosahexaenoic acid (DHA), in brain functions is largely documented. DHA is incorporated into membrane phospholipids as structural component, especially in the central nervous system where it also has important functional effects. The aim of this review is to investigate the relationship between DHA and cognitive function in relation to mental disorders. Results from few randomized controlled trials (RCTs) on the effects of DHA (alone or in combination) in psychotic, mood and neurodevelopmental disorders, respectively, suggest that no conclusive remarks can be drawn.

Anxiety disorders (ADs) are a group of prevalent and destructive mental illnesses, but the current understanding of their underlying neuropathology is still unclear. Employing voxel-based morphometry (VBM), previous studies have demonstrated several common brain regions showing grey matter volume (GMV) abnormalities. However, contradictory results have been reported among these studies. Considering that different subtypes of ADs exhibit common core symptoms despite different diagnostic criteria, and previous meta-analyses have found common core GMV-altered brain regions in ADs, the present research aimed to combine the results of individual studies to identify common GMV abnormalities in ADs. Therefore, we first performed a systematic search in PubMed, Embase, and Web of Science on studies investigating GMV differences between patients with ADs and healthy controls (HCs). Then, the anisotropic effect-size signed differential mapping (AES-SDM) was applied in this meta-analysis. A total of 24 studies (including 25 data sets) were included in the current study, and 906 patients with ADs and 1003 HCs were included. Compared with the HCs, the patients with ADs showed increased GMV in the left superior parietal gyrus, right angular gyrus, left precentral gyrus, and right lingual gyrus, and decreased GMV in the bilateral insula, bilateral thalamus, left caudate, and right putamen. In conclusion, the current study has identified some abnormal GMV brain regions that are related to the pathological mechanisms of anxiety disorders. These findings could contribute to a better understanding of the underlying neuropathology of ADs., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Although it has been consistently reported the important role of genetic and environmental risk factors on structural and functional alterations in Major Depressive Disorder (MDD), the mechanism and the magnitude of the interactions between specific genetic and/or environmental risk factors on brain structures in this disabling disorder are still elusive. Therefore, in the last two decades an increased interest has been devoted to neuroimaging investigations on monozygotic and dizygotic twin samples mainly because their intrinsic characteristics may help to separate the effects of genetic and environmental risk factors on clinical phenotypes, including MDD., Methods: In this context, the present review summarizes results from structural and functional Magnetic Resonance Imaging studies that investigated twin samples in correlation with MDD., Results: Overall the results confirmed that a) MDD is characterized by significant alterations in selective brain areas presiding over emotion recognition and evaluation, including amygdala, insula and prefrontal cortices, and b) both genetic and environmental risk factors play a key role in the pathophysiology of this disorder., Limitations: Few MRI studies exploring MDD in twin samples., Conclusions: The specific contribution of both aspects is still not fully elucidated especially because genes and environment have an impact on the same brain areas, which are particularly vulnerable in MDD. Expansion of the current twin sample sizes would help to clearly establish the potential relationship between risk factors and the development of MDD., (Copyright © 2017 Elsevier B.V. All rights reserved.)

In population neuroscience, three disciplines come together to advance our knowledge of factors that shape the human brain: neuroscience, genetics, and epidemiology (Paus, Human Brain Mapping 31:891-903, 2010). Here, I will come back to some of the background material reviewed in more detail in our previous book (Paus, Population Neuroscience, 2013), followed by a brief overview of current advances and challenges faced by this integrative approach., (© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Background: Although some Magnetic Resonance Imaging (MRI) studies have investigated the relationship between clinical severity and neuroanatomical alterations in patients with schizophrenia (SCZ), the biological signature associated with illness severity in schizophrenia is still uncertain. Therefore, this study aims to investigate structural brain abnormalities in SCZ, with particular regards to the identification of potential deficits associated with the severity of illness., Methods: In total, 1.5T MRI data were acquired for 61 subjects with SCZ and 59 matched healthy controls (HC). The patient group was divided in two sub-groups based on clinical severity, one composed of 34 mild-to-moderately ill patients, and the other of 27 severely ill patients, and compared with matched HC., Results: The whole group of patients with SCZ had significantly reduced grey matter (GM) volumes in the left inferior and middle temporal gyrus compared to HC (p < 0.05, pFWE corrected). Furthermore, compared to HC, patients with mild-to-moderate illness showed decreased GM volumes in the inferior and middle temporal gyrus, whereas those with severe illness had reduced GM volumes in the middle temporal gyrus and cerebellum bilaterally (all p < 0.001 uncorrected). No differences were observed between the two sub-groups of patients., Conclusion: The results showed significant GM volume reductions in temporal regions in patients with SCZ compared to matched HC, confirming the role of these regions in the pathophysiology of SCZ. Furthermore, specific cerebellar grey matter volume reductions were identified in patients with severe illness, which may contribute to stratifying patients with SCZ according to their clinical phenotype expression, ultimately helping in guiding targeted therapeutic/rehabilitation interventions.

Considerable uncertainty exists about the defining brain changes associated with bipolar disorder (BD). Understanding and quantifying the sources of uncertainty can help generate novel clinical hypotheses about etiology and assist in the development of biomarkers for indexing disease progression and prognosis. Here we were interested in quantifying case-control differences in intracranial volume (ICV) and each of eight subcortical brain measures: nucleus accumbens, amygdala, caudate, hippocampus, globus pallidus, putamen, thalamus, lateral ventricles. In a large study of 1710 BD patients and 2594 healthy controls, we found consistent volumetric reductions in BD patients for mean hippocampus (Cohen's d=-0.232; P=3.50 × 10 -7 ) and thalamus (d=-0.148; P=4.27 × 10 -3 ) and enlarged lateral ventricles (d=-0.260; P=3.93 × 10 -5 ) in patients. No significant effect of age at illness onset was detected. Stratifying patients based on clinical subtype (BD type I or type II) revealed that BDI patients had significantly larger lateral ventricles and smaller hippocampus and amygdala than controls. However, when comparing BDI and BDII patients directly, we did not detect any significant differences in brain volume. This likely represents similar etiology between BD subtype classifications. Exploratory analyses revealed significantly larger thalamic volumes in patients taking lithium compared with patients not taking lithium. We detected no significant differences between BDII patients and controls in the largest such comparison to date. Findings in this study should be interpreted with caution and with careful consideration of the limitations inherent to meta-analyzed neuroimaging comparisons.

Polymorphisms at the rs10994336 and rs9804190 loci of the Ankyrin 3 (ANK3) gene have been strongly associated with increased risk for bipolar disorder (BD). However, their potential pathogenetic effect on BD-relevant neural circuits remains unknown. We examined the effect of BD-risk polymorphisms at rs10994336 and rs9804190 on the working memory (WM) circuit using functional magnetic resonance imaging (fMRI) data obtained from euthymic patients with BD (n = 41), their psychiatrically healthy first-degree relatives (n = 25) and unrelated individuals without personal or family history of psychiatric disorders (n = 46) while performing the N-back task. In unrelated healthy individuals, the rs10994336-risk-allele was associated with reduced activation of the ventral visual cortical components of the WM circuit while the rs9804190-risk-allele was associated with inefficient hyperactivation of the prefrontal cortical components of the WM. In patients and their healthy relatives, risk alleles at either loci were associated with hyperactivation in the ventral anterior cingulate cortex. Additionally, Rs9804190-risk-allele carriers with BD evidenced abnormal hyperactivation within the posterior cingulate cortex. This study provides new insights on the neurogenetic correlates of allelic variation at different genome-wide supported BD-risk associated ANK3 loci that support their involvement in BD and highlight the modulatory influence of increased background genetic risk for BD., (© 2015 Wiley Periodicals, Inc.)

The population ageing process worldwide is leading to an increasing number of women in the perimenopausal phase. Many of the perimenopausal symptoms, such as headache, depression, insomnia, and cognitive decline, are neurological in nature. Therefore, the study of the perimenopausal brain is of great importance. In addition, relevant studies can also provide an imaging basis for multiple therapies to treat perimenopausal symptoms. Because of its non-invasive nature, magnetic resonance imaging (MRI) has now been widely applied to the study of perimenopausal brains, revealing alterations in the brain associated with symptoms during the menopause transition. In this review, we collected papers and works of literature on the perimenopausal brain using MRI techniques in the Web of Science database. We firstly described the general principles and analysis methods of different MRI modalities briefly and then reviewed the structural, functional, perfusion, and metabolic compounds changes in the brain of perimenopausal women respectively, and described the latest advances in probing the perimenopausal brain using MRI, resulting in summary diagrams and figures. Based on the summary of existing works of the literature, this review further provided a perspective on multi-modal MRI studies in the perimenopausal brain, suggesting that population-based, multi-center, and longitudinal studies will be beneficial to the comprehensive understanding of changes in the perimenopausal brain. In addition, we found a hint towards neural heterogeneity in the perimenopausal brain, which should be addressed by future MRI studies to provide more help for the precise diagnosis and personalized treatment of perimenopausal symptoms. KEY POINTS: • Perimenopause is not only a physiological transition but also a period of neurological transition. • Multi-modal MRI studies have revealed that perimenopause is accompanied by alterations in the brain, which is implicated in many perimenopausal symptoms. • The diversity in the multi-modal MRI findings may give a hint to neural heterogeneity in the perimenopausal brain., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

There is evidence of genetic polymorphism influences on brain structure and function, genetic risk in bipolar disorder (BD), and neuroimaging correlates of BD. How genetic influences related to BD could be reflected on brain changes in BD has been efficiently reviewed in a 2017 systematic review. We aimed to confirm and extend these findings through a Preferred Reporting Items for Systematic reviews and Meta-Analyses-based systematic review. Our study allowed us to conclude that there is no replicated finding in the timeframe considered. We were also unable to further confirm prior results of the BDNF gene polymorphisms to affect brain structure and function in BD. The most consistent finding is an influence of the CACNA1C rs1006737 polymorphism in brain connectivity and grey matter structure and function. There was a tendency of undersized studies to obtain positive results and large, genome-wide polygenic risk studies to find negative results in BD. The neuroimaging genetics in BD field is rapidly expanding., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

With the emergence of positron emission tomography (PET) in the late 1970s, psychiatry had access to a tool capable of non-invasive assessment of human brain function. Early applications in psychiatry focused on identifying characteristic brain blood flow and metabolic derangements using radiotracers such as [ 15 O]H 2 O and [ 18 F]FDG. Despite the success of these techniques, it became apparent that more specific probes were needed to understand the neurochemical bases of psychiatric disorders. The first neurochemical PET imaging probes targeted sites of action of neuroleptic (dopamine D 2 receptors) and psychoactive (serotonin receptors) drugs. Based on the centrality of monoamine dysfunction in psychiatric disorders and the measured success of monoamine-enhancing drugs in treating them, the next 30 years witnessed the development of an armamentarium of PET radiopharmaceuticals and imaging methodologies for studying monoamines. Continued development of monoamine-enhancing drugs over this time however was less successful, realizing only modest gains in efficacy and tolerability. As patent protection for many widely prescribed and profitable psychiatric drugs lapsed, drug development pipelines shifted away from monoamines in search of novel targets with the promises of improved efficacy, or abandoned altogether. Over this period, PET radiopharmaceutical development activities closely paralleled drug development priorities resulting in the development of new PET imaging agents for non-monoamine targets. Part one of this review will briefly survey novel PET imaging targets with relevance to the field of psychiatry, which include the metabotropic glutamate receptor type 5 (mGluR5), purinergic P 2 X 7 receptor, type 1 cannabinoid receptor (CB 1 ), phosphodiesterase 10A (PDE10A), and describe radiotracers developed for these and other targets that have matured to human subject investigations. Current limitations of the targets and techniques will also be discussed., (© 2022 International Society for Neurochemistry.)

Severe worry is a complex transdiagnostic phenotype independently associated with increased morbidity, including cognitive impairment and cardiovascular diseases. We investigated the neurobiological basis of worry in older adults by analyzing resting state fMRI using a large-scale network-based approach. We collected resting fMRI on 77 participants (>50 years old) with varying worry severity. We computed region-wise connectivity across the default mode network (DMN), anterior salience network, and left executive control network. All 22,366 correlations were regressed on worry severity and adjusted for age, sex, race, education, disease burden, depression, anxiety, rumination, and neuroticism. We employed higher criticism, a second-level method of significance testing for rare and weak features, to reveal the functional connectivity patterns associated with worry. The analysis suggests that worry has a complex, yet distinct signature associated with resting state functional connectivity. Intra-connectivities and inter-connectivities of the DMN comprise the dominant contribution. The anterior cingulate, temporal lobe, and thalamus are heavily represented with overwhelmingly negative association with worry. The prefrontal regions are also strongly represented with a mix of positive and negative associations with worry. Identifying the most salient connections may be useful for targeted interventions for reducing morbidity associated with severe worry in older adults., (© 2021. The Author(s).)

Characterizing the properties of brain networks across mood states seen in bipolar disorder (BP) can provide a deeper insight into the mechanisms involved in this type of affective disorder. In this study, graph theoretical methods were used to examine global, modular and nodal brain network topology in the resting state using functional magnetic resonance imaging data acquired from 95 participants, including those with bipolar depression (BPD; n = 30) and bipolar mania (BPM; n = 39) and healthy control (HC) subjects (n = 26). The threshold value of the individual subjects' connectivity matrix varied from 0.15 to 0.30 with steps of 0.01. We found that: (1) at the global level, BP patients showed a significantly increased global efficiency and synchronization and a decreased path length; (2) at the nodal level, BP patients showed impaired nodal parameters, predominantly within the frontoparietal and limbic sub-network; (3) at the module level, BP patients were characterized by denser FCs (edges) between Module III (the front-parietal system) and Module V (limbic/paralimbic systems); (4) at the nodal level, the BPD and BPM groups showed state-specific differences in the orbital part of the left superior-frontal gyrus, right putamen, right parahippocampal gyrus and left fusiform gyrus. These results revealed abnormalities in topological organization in the whole brain, especially in the frontoparietal-limbic circuit in both BPD and BPM. These deficits may reflect the pathophysiological processes occurring in BP. In addition, state-specific regional nodal alterations in BP could potentially provide biomarkers of conversion across different mood states., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

Childhood trauma is a risk factor for psychotic and mood disorders that is associated with abnormal hypothalamic-pituitary-adrenal (HPA) axis function in response to stress and abnormal social brain function. Here, we aimed to determine whether childhood trauma exposure would differently moderate associations between cortisol reactivity and social brain function, among cases with schizophrenia (SZ), bipolar disorder (BD) and in healthy individuals (HC). Forty cases with SZ, 35 with BD and 34 HCs underwent functional magnetic resonance imaging while performing an emotional face-matching task. Participants completed the Childhood Trauma Questionnaire and cortisol reactivity (i.e. the slope indexing the within-subject difference between pre- and post-imaging salivary cortisol levels) was determined. The severity of childhood trauma moderated the relationship between cortisol reactivity and brain activation in the bilateral temporo-parieto-insular junctions, right middle cingulum, right pre/postcentral gyri, left cerebellum and right lingual gyrus, differently depending on the clinical group. When exposed to high levels of trauma, the cortisol slope was negatively associated with activation in these regions in HC, while the cortisol slope was positively associated with activation in these regions in SZ cases. Similarly, there were differences between the groups in how trauma severity moderated the relationship between cortisol reactivity and functional connectivity between the amygdala and dorsolateral prefrontal cortex. In addition to reflecting typical associations between cortisol reactivity and emotional brain function when not exposed to childhood trauma, these findings provide new evidence that trauma exposure disrupts these relationships in both healthy individuals and in cases with SZ or BD., (© 2020. Springer-Verlag GmbH Germany, part of Springer Nature.)

Despite decades of research, the pathophysiology of bipolar disorder (BD) is still not well understood. Structural brain differences have been associated with BD, but results from neuroimaging studies have been inconsistent. To address this, we performed the largest study to date of cortical gray matter thickness and surface area measures from brain magnetic resonance imaging scans of 6503 individuals including 1837 unrelated adults with BD and 2582 unrelated healthy controls for group differences while also examining the effects of commonly prescribed medications, age of illness onset, history of psychosis, mood state, age and sex differences on cortical regions. In BD, cortical gray matter was thinner in frontal, temporal and parietal regions of both brain hemispheres. BD had the strongest effects on left pars opercularis (Cohen's d=-0.293; P=1.71 × 10-21), left fusiform gyrus (d=-0.288; P=8.25 × 10-21) and left rostral middle frontal cortex (d=-0.276; P=2.99 × 10-19). Longer duration of illness (after accounting for age at the time of scanning) was associated with reduced cortical thickness in frontal, medial parietal and occipital regions. We found that several commonly prescribed medications, including lithium, antiepileptic and antipsychotic treatment showed significant associations with cortical thickness and surface area, even after accounting for patients who received multiple medications. We found evidence of reduced cortical surface area associated with a history of psychosis but no associations with mood state at the time of scanning. Our analysis revealed previously undetected associations and provides an extensive analysis of potential confounding variables in neuroimaging studies of BD.

Background: Borderline personality disorder (BPD) affects 1-5% of the population and is characterized by a complex symptomatology and selective functional impairments. Although brain imaging studies have contributed to better characterizing the pathophysiological mechanisms underlying BPD, the white matter (WM) deficits associated with this disorder are still unclear. Therefore, the present review aims at providing an overview of the findings emerged from the available diffusion tensor imaging (DTI) studies on BPD.Methods: From a bibliographic research in PubMed until May 2019, we collected 12 studies that fulfilled our inclusion criteria, including a total sample of 291 BPD subjects and 293 healthy controls.Results: Overall, the DTI studies reviewed showed impairments in selective WM tracts that are part of the prefronto-limbic system, including frontal WM (short and long tracts), anterior cingulate cortex, corpus callosum, corona radiata, hippocampal fornix and thalamic radiation, in BPD patients compared to healthy controls.Limitations: Few DTI studies with heterogeneous findings.Conclusions: Overall these results reported that BPD is characterized by selective structural connectivity alterations in prefronto-limbic structures, further supporting the neurobiological model of BPD that suggests the presence of an abnormal modulation of frontal regions over limbic structures. Finally, the results also highlighted that the disrupted WM integrity in selective brain regions may also explain key-aspects of BPD symptomatology, including emotional dysregulation, ambivalence, contradictory behaviors and cognitive dysfunctions. [ABSTRACT FROM AUTHOR]

BackgroundSchizophrenia (SZ) and bipolar disorder (BD) may overlap in etiology and phenomenology but differ with regard to emotional processing. We used facial affect as a probe for emotional processing to determine whether there are diagnosis-related differences between SZ and BD in the function of the underlying neural circuitry.MethodFunctional magnetic resonance imaging (fMRI) studies published up to 30 April 2012 investigating facial affect processing in patients with SZ or BD were identified through computerized and manual literature searches. Activation foci from 29 studies encompassing 483 healthy individuals, 268 patients with SZ and 267 patients with BD were subjected to voxel-based quantitative meta-analysis using activation likelihood estimation (ALE).ResultsCompared to healthy individuals, when emotional facial stimuli were contrasted to neutral stimuli, patients with BD showed overactivation within the parahippocampus/amygdala and thalamus and reduced engagement within the ventrolateral prefrontal cortex (PFC) whereas patients with SZ showed underactivation throughout the entire facial affect processing network and increased activation in visual processing regions within the cuneus. Patients with BD showed greater thalamic engagement compared to patients with SZ; in the reverse comparison, patients with SZ showed greater engagement in posterior associative visual cortices.ConclusionsDuring facial affect processing, patients with BD show overactivation in subcortical regions and underactivation in prefrontal regions of the facial affect processing network, consistent with the notion of reduced emotional regulation. By contrast, overactivation within visual processing regions coupled with reduced engagement of facial affect processing regions points to abnormal visual integration as the core underlying deficit in SZ. [ABSTRACT FROM AUTHOR]

The incidence of eating disorders in children, mainly of anorexia nervosa, is dramatically increased in the last years. A timely identification of the disease is associated with higher rates of recovery. Aim of the work is to underline signs and symptoms that can be used to an early detection of anorexia nervosa in the pediatric age. A scoping review has been conducted by The Italian Pediatric Society Adolescent Study Group according to the PRISMA Extension guidelines for Scoping Reviews, using the search term "anorexia nervosa" and the following filters "review", "systematic review", "age 0–18", "last 4 years". The strategy search produced 657 studies, of which 52 were included in this revision. Screening and red flags were discussed in 23 reports, genetics in 12, neurological pathways in 11, environmental factors in 10, and gut microbiota in 7. An accurate physiological and pathological anamnesis, physical and psychological examination, including the body perception, should be taken in account as well as the presence of co-morbidities, including chronic functional abdominal pain and autoimmune/autoinflammatory diseases. Evidence suggests the role of familiar predisposition as well as of neurological morphology and pathway in anorexia nervosa development. Gut microbiota has also been included among possible risk factor for developing anorexia nervosa due to a complex direct and indirect interactions between gut and brain. The Italian Pediatric Society Adolescent Study Group suggests performing an accurate familial and personal anamnesis, including psychological evaluation as well as a physical exam including auxological parameters as a screening tool during pediatric checks to better explore the risk of developing anorexia nervosa. [ABSTRACT FROM AUTHOR]

Background: Functional magnetic resonance imaging studies on emotion processing in patients with bipolar disorder (BD) show hyperactivity of limbic-striatal brain areas and hypoactivity in inferior frontal areas compared to healthy participants. However, heterogeneous results in patients with different disease states and different valences of emotional stimuli have been identified. Methods: To integrate previous results and elucidate the impact of disease state and stimulus valence, we conducted a systematic literature search for journal articles in the Web of Science Core Collection including MEDLINE databases and employed a coordinate-based-meta-analysis of functional-MRI studies comparing emotion processing in BD-patients with healthy participants using seed-based d mapping (SDM) to test for between-subjects-effects. We included 31 studies published before 11/2022 with a total of N = 766 BD-patients and N = 836 controls. Results: Patients with BD showed hyperactivated regions involved in salience processing of emotional stimuli (e.g., the bilateral insula) and hypoactivation of regions associated with emotion regulation (e.g., inferior frontal gyrus) during emotion processing, compared to healthy participants. A more detailed descriptive analysis revealed a hypoactive (anterior) insula in manic BD-patients specifically for negative in comparison to positive emotion processing. Discussion: This meta-analysis corroborates the overall tenor of existing literature that patients with BD show an increased emotional reactivity (hyperactivity of salience-processing regions) together with a lower (cognitive) control (hypoactivity of brain areas associated with emotion regulation) over emotional states. Our analysis suggests reduced interoceptive processing of negative stimuli in mania, pointing out the need for longitudinal within-subject analyses of emotion processing. [ABSTRACT FROM AUTHOR]

Importance: Identifying neurobiological differences between patients with major depressive disorder (MDD) and healthy individuals has been a mainstay of clinical neuroscience for decades. However, recent meta-analyses have raised concerns regarding the replicability and clinical relevance of brain alterations in depression.Objective: To quantify the upper bounds of univariate effect sizes, estimated predictive utility, and distributional dissimilarity of healthy individuals and those with depression across structural magnetic resonance imaging (MRI), diffusion-tensor imaging, and functional task-based as well as resting-state MRI, and to compare results with an MDD polygenic risk score (PRS) and environmental variables.Design, Setting, and Participants: This was a cross-sectional, case-control clinical neuroimaging study. Data were part of the Marburg-Münster Affective Disorders Cohort Study. Patients with depression and healthy controls were recruited from primary care and the general population in Münster and Marburg, Germany. Study recruitment was performed from September 11, 2014, to September 26, 2018. The sample comprised patients with acute and chronic MDD as well as healthy controls in the age range of 18 to 65 years. Data were analyzed from October 29, 2020, to April 7, 2022.Main Outcomes and Measures: Primary analyses included univariate partial effect size (η2), classification accuracy, and distributional overlapping coefficient for healthy individuals and those with depression across neuroimaging modalities, controlling for age, sex, and additional modality-specific confounding variables. Secondary analyses included patient subgroups for acute or chronic depressive status.Results: A total of 1809 individuals (861 patients [47.6%] and 948 controls [52.4%]) were included in the analysis (mean [SD] age, 35.6 [13.2] years; 1165 female patients [64.4%]). The upper bound of the effect sizes of the single univariate measures displaying the largest group difference ranged from partial η2 of 0.004 to 0.017, and distributions overlapped between 87% and 95%, with classification accuracies ranging between 54% and 56% across neuroimaging modalities. This pattern remained virtually unchanged when considering either only patients with acute or chronic depression. Differences were comparable with those found for PRS but substantially smaller than for environmental variables.Conclusions and Relevance: Results of this case-control study suggest that even for maximum univariate biological differences, deviations between patients with MDD and healthy controls were remarkably small, single-participant prediction was not possible, and similarity between study groups dominated. Biological psychiatry should facilitate meaningful outcome measures or predictive approaches to increase the potential for a personalization of the clinical practice. [ABSTRACT FROM AUTHOR]

Background: Subclinical psychotic-like experiences (PLE), resembling key symptoms of psychotic disorders, are common throughout the general population and possibly associated with psychosis risk. There is evidence that such symptoms are also associated with structural brain changes. Methods: In 672 healthy individuals, we assessed PLE and associated distress with the symptom-checklist-90R (SCL-90R) scales 'schizotypal signs' (STS) and 'schizophrenia nuclear symptoms' (SNS) and analysed associations with voxel- and surfaced-based brain structural parameters derived from structural magnetic resonance imaging at 3 T with CAT12. Results: For SNS, we found a positive correlation with the volume in the left superior parietal lobule and the precuneus, and a negative correlation with the volume in the right inferior temporal gyrus [p < 0.05 cluster-level Family Wise Error (FWE-corrected]. For STS, we found a negative correlation with the volume of the left and right precentral gyrus (p < 0.05 cluster-level FWE-corrected). Surface-based analyses did not detect any significant clusters with the chosen statistical threshold of p < 0.05. However, in exploratory analyses (p < 0.001, uncorrected), we found a positive correlation of SNS with gyrification in the left insula and rostral middle frontal gyrus and of STS with the left precuneus and insula, as well as a negative correlation of STS with gyrification in the left temporal pole. Conclusions: Our results show that brain structures in areas implicated in schizophrenia are also related to PLE and its associated distress in healthy individuals. This pattern supports a dimensional model of the neural correlates of symptoms of the psychotic spectrum. [ABSTRACT FROM AUTHOR]

Research has found strong evidence for common and distinct morphometric brain abnormality profiles in nonaffective psychosis (NAff-P) and affective psychosis (Aff-P). Due to chronicity and prolonged medication exposure confounds, it is crucial to examine structural morphometry early in the course of psychosis. Using Human Connectome Project-Early Psychosis data, multivariate profile analyses were implemented to examine regional profiles for cortical thickness, cortical surface area, subcortical volume, and ventricular volume in healthy control (HC; n  = 56), early illness NAff-P (n  = 83), and Aff-P (n  = 30) groups after accounting for normal aging. Associations with symptom severity, functioning, and cognition were also examined. Group regional profiles were significantly nonparallel and differed in level for cortical thickness (P  < .001), with NAff-P having widespread cortical thinning relative to HC and Aff-P and some regions showing greater deficits than others. Significant nonparallelism of group regional profiles was also evident for cortical surface area (P  < .006), with Aff-P and N-Aff-P differing from HC and from each other (P  < .001). For subcortical volume, there was significant profile nonparallelism with NAff-P having an enlarged left pallidum and smaller accumbens and hippocampus (P  < .028), and Aff-P having a smaller accumbens and amygdala (P  < .006), relative to HC. NAff-P also had larger basal ganglia compared to Aff-P. Furthermore, NAff-P had enlarged ventricles (P  < .055) compared to HC and Aff-P. Additionally, greater ventricular volume was associated with increased manic symptoms in NAff-P and Aff-P. Overall, this study found common and distinct regional morphometric profile abnormalities in early illness NAff-P and Aff-P, providing evidence for both shared and disease-specific pathophysiological processes. [ABSTRACT FROM AUTHOR]

Background: Borderline Personality Disorder (BPD) is a severe and disabling psychiatric syndrome, frequently associated with self-injurious behaviours (SIB). In recent years, functional magnetic resonance imaging (fMRI) investigations have tried to identify alterations associated with SIB amongst BPD patients, in order to better delineate possible neurobiological underpinnings of these manifestations. In this mini-review, we aimed at summarizing fMRI studies exploring patterns of neural activation associated with SIB in BPD patients.Methods: Literature searches on PubMed, Psych-Info and Embase databases were performed for all fMRI studies including adult patients with BPD and SIB undergoing different tasks, including painful or thermic stimulation, affective stimulation through the presentation of picturesor the recollection of personal memories as well as tasks that evaluate sustained attention and impulsivity, and reward processing. Thirteen relevant papers were considered eligible for the present review.Results: Patients with BPD and SIB, compared to HC, showed prefrontal, nucleus accumbens overactivation and amygdala deactivation during pain stimulation. During negative affective stimulation, BPD patients showed a hyperactivation of the amygdala and a hypoactivation of the orbitofrontal cortex (OFC), which was also found to be enhanced during a gambling task and during a recalling of aversive memories. In contrast, during cognitive tasks with negative affective interference, BPD patients showed hypoactivation of OFC, anterior cingulated cortex, and basal ganglia.Limitations: The limited number of studies and the heterogeneity regarding the fMRI tasks employed allowed only suggestive conclusions.Conclusions: The reviewed fMRI studies highlighted that BPD patients with a history of SIB showed altered brain activity, compared to HC, in regions involved in inhibitory cognitive processes and affect regulation, which may in turn, explain the overwhelming emotional experiences eliciting SIB in these patients. [ABSTRACT FROM AUTHOR]

The nature of the relationship between cognition and brain morphology in schizophrenia-spectrum disorders (SSD) and bipolar disorder (BD) is uncertain. This review aimed to address this, by providing a comprehensive systematic investigation of links between several cognitive domains and brain volume, cortical thickness, and cortical surface area in SSD and BD patients across early and established illness stages. An initial search of PubMed and Scopus databases resulted in 1486 articles, of which 124 met inclusion criteria and were reviewed in detail. The majority of studies focused on SSD, while those of BD were scarce. Replicated evidence for specific regions associated with indices of cognition was minimal, however for several cognitive domains, the frontal and temporal regions were broadly implicated across both recent-onset and established SSD, and to a lesser extent BD. Collectively, the findings of this review emphasize the significance of both frontal and temporal regions for some domains of cognition in SSD, while highlighting the need for future BD-related studies on this topic. [ABSTRACT FROM AUTHOR]

Objectives: The aim of the study is to assess amide concentration changes in ALS patients compared with healthy controls by using quantitative amide proton transfer (APT) and multiparameter magnetic resonance imaging, and testing its correlation with clinical scores. Methods: Sixteen ALS patients and sixteen healthy controls were recruited as part of the Canadian ALS Neuroimaging Consortium, and multimodal magnetic resonance imaging was performed at 3 T, including APT and diffusion imaging. Lorentz fitting was used to quantify the amide effect. Clinical disability was evaluated using the revised ALS functional rating scale (ALSFRS-R), and its correlation with image characteristics was assessed. The diagnostic performance of different imaging parameters was evaluated with receiver operating characteristic analysis. Results: Our results showed that the amide peak was significantly different between the motor cortex and other gray matter territories within the brain of ALS patients (p < 0.001). Compared with controls, amide signal intensities in ALS were significantly reduced in the motor cortex (p < 0.001) and corticospinal tract (p = 0.046), while abnormalities were not detected using routine imaging methods. There was no significant correlation between amide and ALSFRS-R score. The diagnostic accuracy of the amide peak was superior to that of diffusion imaging. Conclusions: This study demonstrated changes of amide signal intensities in the motor cortex and corticospinal tract of ALS patients. Key Points: • The neurodegenerative disease amyotrophic lateral sclerosis (ALS) has a lack of objective imaging indicators for diagnosis and assessment. • Analysis of amide proton transfer imaging revealed changes in the motor cortex and corticospinal tract of ALS patients that were not visible on standard magnetic resonance imaging. • The diagnostic accuracy of the amide peak was superior to that of diffusion imaging. [ABSTRACT FROM AUTHOR]

Depression frequently occurs in first-episode psychosis (FEP) and predicts longer-term negative outcomes. It is possible that this depression is seen primarily in a distinct subgroup, which if identified could allow targeted treatments. We hypothesize that patients with recent-onset psychosis (ROP) and comorbid depression would be identifiable by symptoms and neuroanatomical features similar to those seen in recent-onset depression (ROD). Data were extracted from the multisite PRONIA study: 154 ROP patients (FEP within 3 months of treatment onset), of whom 83 were depressed (ROP+D) and 71 who were not depressed (ROP−D), 146 ROD patients, and 265 healthy controls (HC). Analyses included a (1) principal component analysis that established the similar symptom structure of depression in ROD and ROP+D, (2) supervised machine learning (ML) classification with repeated nested cross-validation based on depressive symptoms separating ROD vs ROP+D, which achieved a balanced accuracy (BAC) of 51%, and (3) neuroanatomical ML-based classification, using regions of interest generated from ROD subjects, which identified BAC of 50% (no better than chance) for separation of ROP+D vs ROP−D. We conclude that depression at a symptom level is broadly similar with or without psychosis status in recent-onset disorders; however, this is not driven by a separable depressed subgroup in FEP. Depression may be intrinsic to early stages of psychotic disorder, and thus treating depression could produce widespread benefit. [ABSTRACT FROM AUTHOR]

Persons with schizophrenia exhibit sensitivity to stress and negative affect (NA), both strongly correlated with poor functional outcome. This theoretical review suggests that NA reflects a "fragile brain," ie, vulnerable to stress, including events not experienced as stressful by healthy individuals. Based on postmortem evidence of altered gamma-aminobutyric acid (GABA) function in parvalbumin positive interneurons (PVI), animal models of PVI abnormalities and neuroimaging data with GABAergic challenge, it is suggested that GABAergic disruptions weaken cortical regions, which leads to stress vulnerability and excessive NA. Neurocircuits that respond to stressful and salient environmental stimuli, such as the hypothalamic-pituitary-adrenal axis and the amygdala, are highly dysregulated in schizophrenia, exhibiting hypo- and hyper-activity. PVI abnormalities in lateral prefrontal cortex and hippocampus have been hypothesized to affect cognitive function and positive symptoms, respectively; in the medial frontal cortex (dorsal anterior cingulate cortex and dorsal medial prefrontal cortex), these abnormalities may lead to vulnerability to stress, NA and dysregulation of stress responsive systems. Given that postmortem PVI disruptions have been identified in other conditions, such as bipolar disorder and autism, stress vulnerability may reflect a transdiagnostic dimension of psychopathology. [ABSTRACT FROM AUTHOR]

Abstract: Rationale, aims, and objectives: In this study, we have attempted to replicate the findings of altered emotional processing in depressed patients compared with healthy controls by means of functional magnetic resonance imaging during passive viewing of positive, negative, and neutral pictures from the International Affective Pictures System. Methods: Nineteen medicated depressed patients and 19 sex and age‐matched healthy controls underwent functional magnetic resonance imaging during presentation of affective pictures in a block design. The differences between the blood oxygen level dependent signal elicited in the tree conditions were compared. Within‐group and between‐group analyses were performed with stringent criteria for statistical inference (P < .05 with family‐wise error correction). Results: In medicated depressed patients, positive pictures compared with neutral pictures activated predominantly the posterior cingulate cortex and precuneus, as well as occipital and middle temporal areas mainly on the left side, while in healthy controls, only the occipito‐temporal areas demonstrated significant activation. The negative pictures elicited stronger activation of occipital and temporal regions in both groups and of inferior frontal gyrus only in control subjects. The difference between the groups did not reach statistical significance. Positive correlation was demonstrated between activation levels of clusters located in left precuneus/posterior cingulate cortex and left inferior/middle occipital gyrus and Montgomery‐Asberg Depression Rating Scale scores in patients while viewing positive compared with neutral pictures. Conclusions: Although the within‐group analysis demonstrated significant activations in both groups with apparent discrepancies, the between‐group analysis did not reach statistical significance under the stringent criteria for statistical inference. These results are further contextualized in the critical debate on the methodological issues of clinical evaluation in psychiatry, more specifically the validity and consistency of the applied methods and the limitations existing in the attempts to provide sound cross‐disciplinary validation of the diagnostic tools by means of neuroscience. [ABSTRACT FROM AUTHOR]

Stress is associated with a greater risk for various health problems including reduced gray matter volume (GMV) and density in a number of brain regions. Previous studies show that neuroimaging could be a means to objectively evaluate stress. However, to date, no definite neuroimaging-derived measures are available to detect stress. In this research we used the gray-matter brain healthcare quotient (GM-BHQ), an MRI-based quotient for monitoring brain health based on GMV, as an objective scale to measure the association of stress with the whole brain. We recruited 63 healthy adults to acquire structural T1-weighted images and stress levels evaluated using three representative stress scales: the Profile of Mood States (POMS), Perceived Stress Scale (PSS) and Chalder Fatigue Scale (CFS). We found that the GM-BHQ was sensitive to fatigue and the interaction between fatigue and stress. [ABSTRACT FROM AUTHOR]

Introduction: Although schizophrenia (SCZ) and bipolar disorder (BD) share elements of pathology, their neural underpinnings are still under investigation. Here, structural Magnetic Resonance Imaging (MRI) data collected from a large sample of BD and SCZ patients and healthy controls (HC) were analyzed in terms of gray matter volume (GMV) using both voxel based morphometry (VBM) and a region of interest (ROI) approach. Methods: The analysis was conducted on two datasets, Dataset1 (802 subjects: 243 SCZ, 176 BD, 383 HC) and Dataset2, a homogeneous subset of Dataset1 (301 subjects: 107 HC, 85 BD and 109 SCZ). General Linear Model analyses were performed 1) at the voxel-level in the whole brain (VBM study), 2) at the regional level in the anatomical regions emerged from the VBM study (ROI study). The GMV comparison across groups was integrated with the analysis of GMV correlates of different clinical dimensions. Results: The VBM results of Dataset1 showed 1) in BD compared to HC, GMV deficits in right cingulate, superior temporal and calcarine cortices, 2) in SCZ compared to HC, GMV deficits in widespread cortical and subcortical areas, 3) in SCZ compared to BD, GMV deficits in insula and thalamus (p<0.05, cluster family wise error corrected). The regions showing GMV deficits in the BD group were mostly included in the SCZ ones. The ROI analyses confirmed the VBM results at the regional level in most of the clusters from the SCZ vs. HC comparison (p<0.05, Bonferroni corrected). The VBM and ROI analyses of Dataset2 provided further evidence for the enhanced GMV deficits characterizing SCZ. Based on the clinical-neuroanatomical analyses, we cannot exclude possible confounding effects due to 1) age of onset and medication in BD patients, 2) symptoms severity in SCZ patients. Conclusion: Our study reported both shared and specific neuroanatomical characteristics between the two disorders, suggesting more severe and generalized GMV deficits in SCZ, with a specific role for insula and thalamus. [ABSTRACT FROM AUTHOR]

Translation as a notion and procedure is deeply embodied in medical science and education. Translation includes the possibility to translate data across disciplines to improve diagnosis and treatment procedures. The evidence accumulated using translation serves as a vehicle for reification of medical diagnoses. There are promising, established post hoc correlations between the different types of clinical tools (interviews and inventories) and neuroscience. The various measures represent statistical correlations that must now be integrated into diagnostic standards and procedures but this, as a whole, is a step forward towards a better understanding of the mechanisms underlying psychopathology in general and depression in particular. Here, we focus on functional magnetic resonance imaging studies using a trans-disciplinary approach and attempt to establish bridges between the different fields. We will selectively highlight research areas such as imaging genetics, imaging immunology and multimodal imaging, as related to the diagnosis and management of depression. [ABSTRACT FROM AUTHOR]

BackgroundResearch in bipolar disorder (BD) implicates fronto-limbic-striatal dysfunction during face emotion processing but it is unknown how such dysfunction varies by task demands, face emotion and patient age.MethodDuring functional magnetic resonance imaging (fMRI), 181 participants, including 62 BD (36 children and 26 adults) and 119 healthy comparison (HC) subjects (57 children and 62 adults), engaged in constrained and unconstrained processing of emotional (angry, fearful, happy) and non-emotional (neutral) faces. During constrained processing, subjects answered questions focusing their attention on the face; this was processed either implicitly (nose width rating) or explicitly (hostility; subjective fear ratings). Unconstrained processing consisted of passive viewing.ResultsPediatric BD rated neutral faces as more hostile than did other groups. In BD patients, family-wise error (FWE)-corrected region of interest (ROI) analyses revealed dysfunction in the amygdala, inferior frontal gyrus (IFG), anterior cingulate cortex (ACC) and putamen. Patients with BD showed amygdala hyperactivation during explicit processing (hostility ratings) of fearful faces and passive viewing of angry and neutral faces but IFG hypoactivation during implicit processing of neutral and happy faces. In the ACC and striatum, the direction of dysfunction varied by task demand: BD demonstrated hyperactivation during unconstrained processing of angry or neutral faces but hypoactivation during constrained processing (implicit or explicit) of angry, neutral or happy faces.ConclusionsFindings suggest amygdala hyperactivation in BD while processing negatively valenced and neutral faces, regardless of attentional condition, and BD IFG hypoactivation during implicit processing. In the cognitive control circuit involving the ACC and putamen, BD neural dysfunction was sensitive to task demands. [ABSTRACT FROM PUBLISHER]

Neuroimaging studies have generated a large body of knowledge regarding the neural correlates of schizophrenia (SZ) and bipolar disorder (BD). However, the initial goal of identifying disease-specific topographical mappings to localized brain regions or to distinct neural networks has not materialized and may be untenable. This contribution will argue that a systems neuroscience approach may prove more fruitful. The supporting evidence presented covers (a) brain structural, functional, and connectivity alterations and their implication for the clinical and cognitive manifestations of SZ and BD, (b) the prevailing system neuroscience models of the 2 disorders, and (c) key hypotheses likely to produce new insights into the mechanisms of underlying psychotic disorders. [ABSTRACT FROM PUBLISHER]