Diagnostic Entity Research Articles

The Capicua C1 Domain is Required for Full Activity of the CIC::DUX4 Fusion Oncoprotein.

Rearrangements between genes can yield neomorphic fusions that drive oncogenesis. Fusion oncogenes are made up of fractional segments of the partner genes that comprise them, with each partner potentially contributing some of its own function to the nascent fusion oncoprotein. Clinically, fusion oncoproteins driving one diagnostic entity are typically clustered into a single molecular subset and are often treated a similar fashion. However, knowledge of where specific fusion breakpoints occur in partner genes, and the resulting retention of functional domains in the fusion, is an important determinant of fusion oncoprotein activity and may differ between patients. This study investigates this phenomena through the example of CIC::DUX4, a fusion between the transcriptional repressor capicua (CIC) and the double homeobox 4 gene (DUX4), which drives an aggressive subset of undifferentiated round cell sarcoma. Using a harmonized dataset of over 100 patient fusion breakpoints from the literature, we show that most bona fide CIC::DUX4 fusions retain the C1 domain, which is known to contribute to DNA binding by wild type CIC. Mechanistically, deletion or mutation of the C1 domain reduces, but does not eliminate, activation of CIC target genes by CIC::DUX4. We also find that expression of C1-deleted CIC::DUX4 is capable of exerting intermediate transformation-related phenotypes compared with those imparted by full-length CIC::DUX4, but was not sufficient for tumorigenesis in a subcutaneous mouse model. In summary, our results suggest a supercharging role for the C1 domain in the activity of CIC::DUX4.

Laser Capture Microdissection of Tertiary Lymphoid Structures from Formalin-Fixed Paraffin-Embedded Sections of Canine Cutaneous and Subcutaneous Sarcomas for NanoString Direct RNA Counting.

Laser capture microdissection (LCM) of formalin-fixed, paraffin-embedded sections is a way to analyze gene expression of morphologically distinct areas of tissue, as microscopically visualized with stained tissue sections. Herein, I describe a method for laser dissecting lymphoid aggregates in canine cutaneous and subcutaneous sarcomas and their adjacent sarcoma tissue to determine the differential expression of RNA as determined by NanoString® nCounter technology. Canine soft tissue sarcomas (STS) are diversely derived mesenchymal neoplasms that, regardless of exact histogenesis, behave similarly and thus have been grouped together as a diagnostic entity. The risk of recurrence and/or metastasis depends on the extent of surgical excision and histologic grade. Lymphoid aggregates are described in these tumors but have not been characterized. In humans, lymphoid aggregates characterized as tertiary lymphoid structures (TLS) improve the prognosis of several tumors, including sarcomas. We sought to determine if RNA expressed by lymphoid aggregates in canine sarcomas was compatible with TLS RNA expression. This chapter describes tissue preparation, staining, laser capture microdissection, and RNA isolation in preparation for digital RNA counting.

Exploring heterogeneity in mild cognitive impairment.

Mild cognitive impairment (MCI) is a heterogeneous diagnostic entity, without a clear prognosis, often accompanied by psychiatric symptomatology and physical frailty. Understanding the heterogeneity within MCI is a critical step in improving the early detection of cognitive decline and developing effective interventions. Cross-sectional multivariate latent mixture analyses of data from patients evaluated between 2015 and 2019, who were routinely entered into a multidisciplinary database for research purposes. A sample of 538 community-dwelling older adults drawn from a large academic medical center, referred from within the Department of Neurology (63.7% Female, Mage = 67.8, SDage = 10.6). Participants completed comprehensive neuropsychological assessments, psychiatric symptom measures, and frailty evaluations. Latent profile analyses supported five profiles of cognitive impairment: At-Risk, Pre-MCI, Amnestic MCI, Multiple Domain MCI, and Major Cognitive Impairment. The inclusion of concomitant psychiatric symptoms and frailty criteria revealed two additional profiles: Psychiatric/Frail, without cognitive impairments, and Multiple Cognitive Domains/Psychiatric/Frail. Critically, 55% of those classified as Healthy based on cognitive data alone were reclassified. Significant profile-wise differences emerged across auxiliary variables of brief cognitive screening, sociodemographics, and medical and psychosocial risk. Results highlight heterogeneity represented by neurologic patients referred for neuropsychological evaluation that include key physical and emotional symptoms known to increase the risk of cognitive decline. Findings are in alignment with more recent research suggesting that the traditional paradigm cognitive impairment may need to be expanded to improve diagnostic accuracy and to develop more tailored, precision-driven interventions.

A deep-learning-based histopathology classifier for focal cortical dysplasia (FCD) unravels a complex scenario of comorbid FCD subtypes.

Recently, we developed a first artificial intelligence (AI)-based digital pathology classifier for focal cortical dysplasia (FCD) as defined by the ILAE classification. Herein, we tested the usefulness of the classifier in a retrospective histopathology workup scenario. Eighty-six new cases with histopathologically confirmed FCD ILAE type Ia (FCDIa), FCDIIa, FCDIIb, mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE), or mild malformations of cortical development were selected, 20 of which had confirmed gene mosaicism. The classifier always recognized the correct histopathology diagnosis in four or more 1000 × 1000-μm digital tiles in all cases. Furthermore, the final diagnosis overlapped with the largest batch of tiles assigned by the algorithm to one diagnostic entity in 80.2% of all cases. However, 86.2% of all cases revealed more than one diagnostic category. As an example, FCDIIb was identified in all of the 23 patients with histopathologically assigned FCDIIb, whereas the classifier correctly recognized FCDIIa tiles in 19 of these cases (83%), that is, dysmorphic neurons but no balloon cells. In contrast, the classifier misdiagnosed FCDIIb tiles in seven of 23 cases histopathologically assigned to FCDIIa (33%). This mandates a second look by the signing histopathologist to either confirm balloon cells or differentiate from reactive astrocytes. The algorithm also recognized coexisting architectural dysplasia, for example, vertically oriented microcolumns as in FCDIa, in 22% of cases classified as FCDII and in 62% of cases with MOGHE. Microscopic review confirmed microcolumns in the majority of tiles, suggesting that vertically oriented architectural abnormalities are more common than previously anticipated. An AI-based diagnostic classifier will become a helpful tool in our future histopathology laboratory, in particular when large anatomical resections from epilepsy surgery require extensive resources. We also provide an open access web application allowing the histopathologist to virtually review digital tiles obtained from epilepsy surgery to corroborate their final diagnosis.

Hemophagocytic Lymphohistiocytosis as an Unusual Presentation in a Patient with Human Immunodeficiency Virus-associated Bone Marrow Classic Hodgkin Lymphoma: A Case Report with Literature Review

Abstract Introduction/Objective Compared to the general population, people living with human immunodeficiency virus (HIV) have a higher incidence of lymphoproliferative disorders including classic Hodgkin lymphoma (CHL). Hemophagocytic lymphohistiocytosis (HLH) triggers in HIV patients include HIV itself and HIV-associated malignancies or infections, all of which can have many overlapping symptoms, causing diagnostic challenges and delays in initiating treatments. Methods/Case Report A 56-year-old HIV-positive man presented with septic shock-like symptoms, pancytopenia, hyperferritinemia, transaminitis, elevated IL2-receptor alpha and hepatomegaly. Mild retroperitoneal lymphadenopathy found on imaging yielded non-diagnostic biopsies. A bone marrow (BM) biopsy showed no malignancy or disseminated infections and a rare hemophagocyte. Treatment for HIV-triggered HLH lead to a marked clinical improvement. Three months later he presented with worsening symptoms, negative cultures, and an EBV+ CHL on a BM biopsy. Mild increase in lymphadenopathy and multiple liver/spleen hypodensities found on imaging could not be biopsied due to rapidly deteriorating patient’s condition and death. Results (if a Case Study enter NA) NA Conclusion Per studies, HLH is more frequent in the HIV-associated lymphomas compared to the non-HIV- associated ones, usually presenting as a sepsis-like syndrome in these patients. Probability of HLH development was particularly high with BM involvement and CHL. From 2010, seven cases of HIV-associated CHL presenting with HLH were found in the literature with these findings: (n=8, including ours) sex- all males; average age- 45 years (range 28- 64); average HIV viral loads- 83,369 copies/mL (range: undetectable->300,000); average absolute CD4 count- 98 cells/microliter (range: 8-314); interval from HIV diagnosis- new to 26 years; anti-retroviral treatment- 6; symptoms- fever (all), other symptoms were variable; HLH-2004 protocol criteria- all; biopsy-proven hemophagocytes- 3; EBV+ CHL- all (6 were diagnosed on BM biopsies); outcomes- remission (2), response to treatment (4), death (2). CHL- triggered HLH in HIV patients is a complex diagnostic entity. A high index of suspicion and thorough investigations including early BM biopsies can ensure better outcomes.

Controversies in trauma- and stress-related disorders.

The release of ICD-11 has resulted in an expansion of diagnostic entities for trauma- and stress-related disorders. This resulted, at least temporarily, in discrepancies with the DSM-5. This situation is outlined and a look is taken at the potential diagnosis of 'continuous traumatic stress reaction'.

Detection and Interpretation of Clonal Hematopoiesis Variants during Routine Solid Tumor Next-Generation Sequencing: A Single-Institution Experience

Clonal hematopoiesis (CH) and Clonal Cytopenia of Undetermined Significance (CCUS) are recently recognized diagnostic entities that serve as an independent risk factor for cardiovascular disease and myeloid malignancy. CH is an incidental finding and evaluation of the incidence of CH/CCUS associated mutations in solid tumor Next Generation Sequencing (NGS) samples was undertaken to better understand the prevalence of mutations in this population. A retrospective review of clinical sequencing data for solid tumor malignancies diagnosed February 2022-April 2023 on NGS data was performed. Cases were reviewed for variants in genes associated with CH/CCUS. Variant allele frequencies and other factors of the sequencing data were assessed for determining risk of CH/CCUS. 2,479 cases were evaluated during the study period. Of these, 29 cases demonstrated potential CH/CCUS associated mutations with a total of 33 variants identified. These were identified in a variety of tumor types, with gliomas being the most common. Significant cardiac histories were found in over half of cases identified and few cases had abnormal blood counts. Detailed criteria for flagging variants as suspicious for CH and recommend these criteria as future guidelines for reporting are described. These variants are incidental findings which require more extensive follow up or change in therapy management utilizing a single institutional cohort.

Reevaluating ADHD and its First-Line Treatment: Insights from DSM-5-TR and Modern Approaches.

Is Attention Deficit Hyperactivity Disorder (ADHD) a "brain disorder"? Should it be managed regularly with stimulant drugs? This article critically examines the evolving biomedical discourse surrounding these questions through a close inspection of the latest edition of the influential psychiatric manual - the DSM-5-TR - as well as additional authoritative sources (e.g., previous DSM editions, consensus statements, FDA communications). The DSM-5-TR acknowledges that "no biological marker is diagnostic for ADHD" and that "meta-analyses of all neuroimaging studies do not show differences between individuals with ADHD and control subjects." The authors of the DSM-5-TR, therefore, conclude that "until these issues are resolved, no form of neuroimaging can be used for diagnosis of ADHD." These statements, along with biases in the neuroimaging literature and additional empirical evidence presented in the article, challenge popular myths about the neurobiological basis of ADHD. Similarly, common beliefs about the first-line treatment of ADHD with stimulant drugs are being increasingly questioned today. For instance, the DSM-5-TR's section on Stimulant-Related Disorders introduces a new diagnostic entity named: Stimulant-Induced Mild Neurocognitive Disorder. This addition aligns with a recent FDA Drug Safety Communication for "all prescription stimulants," which highlights longstanding concerns regarding the safety of medications prescribed to millions of diagnosed individuals, primarily children. The FDA now mandates that "the Boxed Warning, FDA's most prominent warning, will describe the risks of misuse, abuse, addiction, and overdose," emphasizing that such "misuse and abuse of prescription stimulants can result in overdose and death." In light of these challenges to the biomedical discourse, this article offers a neurodiversity-oriented alternative. Using evolutionary principles and historical context, it argues that most cases of ADHD fall under the DSM's socio-philosophical category of "conflicts that are primarily between the individual and society" (similar to homosexuality, which was removed from the DSM in 1973), and are therefore "not mental disorders".

Cerebral salt wasting syndrome in an elderly patient with cerebral small vessel disease.

Hyponatremia is a common electrolyte disturbance seen among the acute geriatric admissions with two common diagnostic entities; the syndrome of inappropriate antidiuretic hormone (SIADH) and cerebral salt wasting syndrome (CSWS) that have different clinical and biochemical presentations, different pathogenesis and therapeutic approaches. Hyponatremia caused by CSWS in patients with cerebral small vessel disease (cSVD) a prevalent condition among the elderly, can be masked in geriatric patients with concomitant fluctuating neurological deficits. Correct diagnosis is crucial to appropriate management. In this case report we describe an association between hyponatremia caused by CSWS in a patient with cSVD.

Understanding splenic B-cell lymphoma/leukaemia with prominent nucleoli: Diagnosis, underpinnings for disease classification and future directions.

The 5th edition of the WHO classification of haematolymphoid tumours (WHO-HAEM5) introduced a new category, splenic B-cell lymphoma/leukaemia with prominent nucleoli (SBLPN). The diagnostic entity B-cell prolymphocytic leukaemia (B-PLL) has been discontinued and the category of hairy cell leukaemia variant (HCLv) has been conceptually reframed. B-PLL and HCLv diagnoses were uncommon. Overlap existed between B-PLL and other indolent lymphomas like chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL). HCLv lacked consistent cytomorphological, immunophenotypic and genetic features. To address these issues, the WHO-HAEM5 classification has introduced SBLPN to serve as a temporary holding ground for entities that do not neatly fit into the existing classification. Cases previously classified as CD5-negative B-PLL and HCLv fall under the SBLPN category. Some splenic marginal zone lymphoma and splenic diffuse red pulp small B-cell lymphoma cases with higher number of medium or large nucleolated B cells would also be classified as SBLPN under the WHO-HAEM5. This review explores the rationale for discontinuing B-PLL and HCLv diagnoses. It then examines the concept of SBLPN, offers practical guidance for diagnosis and discusses future directions in classifying splenic B-cell lymphomas.

Periodic Catatonia: A Tangled Spectra within Neuropsychiatry

Catatonia was first described by Kahlbaum in 1874. Subsequently, in 1908, Kraepelin delineated a cyclical pattern of catatonia in a group of patients with Schizophrenia. Further ahead, in 1938, Gjessing demonstrated the role of nitrogen phasic change in synchronous syntonic cases of periodic catatonia. However, Stokes et al., in 1941, demonstrated it to be a result of steady accumulation rather than a phasic change in nitrogen balance. There are no reliable prevalence figures for periodic catatonia. Prominent diagnostic manuals have not given this diagnostic entity a separate nosological status, despite evidence of a discrete metabolic profile. This case series elucidates periodic catatonia in different psychiatric disorders and how a separate diagnostic criterion could help in early detection and management. We narrate three case reports of catatonic manifestations in two young adolescents and one young adult male, with no underlying medical condition. The first case report highlights intermittent brief periods of catatonic excitement beginning with acute anxiety and followed by fainting spells. The second case report narrates an acute onset manic episode which alternates with the catatonic episode. The third case report shows seasonal advents of catatonia. The pharmacological intervention itself was adequate enough to resolve the catatonic symptoms. The three cases give a purview of catatonic manifestations with differential phenomenology. The treatment of catatonia bears challenges owing to a lack of awareness and differential response to available pharmacotherapy.

Quo vadis DSM-6? An expert survey on the classification, diagnosis, and differential diagnosis of body-focused repetitive behaviors

BackgroundMany conditions we now call body-focused repetitive behaviors (BFRBs) have been subject to research for several decades, most notably trichotillomania and skin picking. However, the American Psychiatric Association did not combine these conditions into a single category, body-focused repetitive behavior disorder (BFRBD), until the fifth edition of the DSM (2013). Several aspects of the disorder remain uncertain and debatable. For example, ongoing debate surrounds which specific conditions fall under this diagnostic category and how to best differentiate BFRBs from conditions such as nonsuicidal self-injury (NSSI). The current article presents results from a study of experts' opinions on diagnostic criteria and descriptions, with the goal of refining the diagnostic criteria. MethodWe contacted experts on BFRB via various sources and invited them to an online survey on the phenomenology, classification, and differential diagnosis of BFRB. We also asked about possible alternative syndrome labels (e.g., body-focused habit). ResultsData from the final sample of 50 experts demonstrates that most experts agree with the present classification of BFRB as an obsessive-compulsive and related disorder and recommend retaining the labels BFRB or BFRBD. The experts considered the following conditions BFRB, with an agreement of over 60 %: trichotillomania, skin picking, dermatophagia, nail biting, and lip-cheek biting. Mixed results emerged for awake bruxism and thumb sucking in adults. In contrast, only a minority regarded night bruxism and knuckle cracking as BFRB. To differentiate BFRB from NSSI, the experts noted that the motive behind the urge (self-harm/injury versus release of tension) should be considered. Analyses of a sub-sample of experts with at least six years of clinical and/or research experience yielded results compatible with those of the entire sample. DiscussionThe survey supports the usefulness of the BFRB or BFRBD diagnostic entity. However, some criteria require further refinement. Future editions of the DSM should more explicitly delineate which conditions qualify as BFRB. Furthermore, it is important to give more attention to the primary motivation behind BFRB to distinguish it from NSSI and potentially from stereotypic movement behavior.

Actualización en el diagnóstico y tratamiento de las obesidades infantiles

The high prevalence of overweight and obesity in the infant and adolescent population has resulted in the latter being one of the most frequent reasons for consultation in our country in Pediatric Offices, both in primary care and in hospital care, as well as for referral for specialized evaluation in pediatric endocrinology consultations. In addition, the increasingly frequent development of very severe (even extreme) forms of obesity before reaching adulthood, in many cases with early onset including even from the first months of life, has led to increased research efforts aimed not only to the diagnosis of specific etiological entities underlying the excessive accumulation of adipose tissue, but also to the development of pharmacological treatments applicable to the different etiologies of the disease during the pediatric age. These pharmacological treatments necessarily need to be accompanied by correction of the imbalance between energy intake and expenditure present in almost all children and adolescents suffering from obesity by modifications in diet and exercise. This article will update the diagnostic strategies available to establish the etiological differential etiological diagnosis of the different childhood and adolescent obesities, whether they are caused by genetic (syndromic or not), endocrinological, or secondary to other underlying conditions. We will also review the current status of the therapeutic options available in the pediatric age group for the treatment of obesity with particular emphasis on the pharmacological treatments available, either specifically in the presence of well-defined diagnostic entities or non-specifically, in the absence of a confirmatory etiological diagnosis.

Disruptive mood dysregulation disorder, parental stress, and attachment styles

Disruptive mood dysregulation disorder (DMDD) is a relatively new diagnostic entity concerning children with chronic irritability and severe anger outbursts. Currently, there is limited knowledge about the parental factors associated with the disorder. The aim of this study was to compare stress levels and attachment styles in parents of children with DMDD with those of parents of children with other diagnoses. Our sample consisted of 218 children (6–12 years, Mage = 9.68 years) referred to child mental health outpatient clinics. Clinicians used a standardized semi-structured diagnostic interview to identify diagnoses. Parental stress levels and attachment styles were assessed using parent reports. We found that parents of children with DMDD experience significantly higher levels of parenting stress related to factors in the child than parents of children with other diagnoses. Furthermore, parents of children with DMDD show a higher association with insecure adult attachment styles than parents of children without DMDD. Finally, an adult preoccupied-ambivalent attachment style explains the variability in parental stress in the DMDD group to a large degree. We discuss how parental stress and an insecure attachment style can be associated with negative parenting practices. An implication from this study could be that treatment results might be improved by involving parents more in treatment programs for children with DMDD.

Comorbidity of bipolar disorder and borderline personality disorder: Phenomenology, course, and treatment considerations.

Bipolar disorder (BD) and borderline personality disorder (BPD) are both serious psychiatric conditions that elevate the risk for harmful outcomes. Although these conditions represent distinct diagnostic entities, existing research suggests that approximately 20% of individuals with BD meet the criteria for comorbid BPD. Individuals with comorbid BD/BPD appear to have a markedly more severe and phenomenologically distinct clinical course when compared with those with BD alone. However, treatments have generally not been tested in this specific population, and currently, no formal treatment guidelines exist for this subgroup of patients. In the current paper, we review the epidemiological and descriptive research characterizing those with comorbid BD/BPD and discuss the impact of this comorbidity on psychosocial treatment. We also review current findings on evidence-based treatments for BD and BPD that show promise in treating those with comorbid BD/BPD. In our review of the literature, we highlight the importance of recognizing this comorbidity and discuss avenues for developing and integrating evidence-based treatment approaches for this understudied clinical population. Although formal trials of interventions targeted to comorbid BD/BPD are limited, there is promising evidence regarding the possibility of using or integrating existing evidence-based approaches for this population. There are also several areas of clinical practice improvement and future research directions that stem from this literature.

Genotype Phenotype Correlation of Renal Tumors in the Cancer Genome Atlas Database.

Morphological features are critical in evaluation of renal tumors and directing molecular workup. The objective of this study was to review histomorphology of renal tumors with molecular alterations of known subtypes. Renal tumors in The Cancer Genome Atlas were reviewed to identify tumors with defining molecular alterations. Single representative digital slides and pathology reports were reviewed and morphologic features recorded. Sixty tumors were identified with molecular alterations in genes characteristic of defined renal cell carcinoma (RCC) subtypes. Findings included the presence of both low- and high-grade histology in TFE3 rearranged RCCs, TFEB amplified RCCs, succinate dehydrogenase (SDH) mutated RCCs and RCCs with mutations in mismatch repair genes. Three ELOC mutated RCCs were identified, one of which demonstrated infiltrative features. Pseudostratification of nuclei in fumarate hydratase mutated RCCs and nuclear grooves in SDH mutated RCCs were intriguing findings not previously reported. Mucinous features were noted in NF2, KRAS, and SDH mutated and ALK rearranged tumors. Significant morphologic overlap was noted across most categories with limited clues for subclassification. Whereas the number of diagnostic entities for kidney tumors continues to increase, many of these have overlapping features, highlighting the significant role molecular characterization currently plays and will continue to play in the future.

Interstitial Lung Diseases and Non-Small Cell Lung Cancer: Particularities in Pathogenesis and Expression of Driver Mutations.

Interstitial lung diseases are a varied group of diseases associated with chronic inflammation and fibrosis. With the emerging and current treatment options, survival rates have vastly improved. Having in mind that the most common type is idiopathic pulmonary fibrosis and that a significant proportion of these patients will develop lung cancer as the disease progresses, prompt diagnosis and personalized treatment of these patients are fundamental. The scope of this review is to identify and characterize molecular and pathogenetic pathways that can interconnect Interstitial Lung Diseases and lung cancer, especially driver mutations in patients with NSCLC, and to highlight new and emerging treatment options in that view. Common pathogenetic pathways have been identified in sites of chronic inflammation in patients with interstitial lung diseases and lung cancer. Of note, the expression of driver mutations in EGFR, BRAF, and KRAS G12C in patients with NSCLC with concurrent interstitial lung disease is vastly different compared to those patients with NSCLC without Interstitial Lung Disease. NSCLC in patients with Interstitial Lung Disease is a challenging diagnostic and clinical entity, and a personalized medicine approach is fundamental to improving survival and quality of life. Newer anti-fibrotic medications have improved survival in IPF/ILD patients; thus, the incidence of lung cancer is going to vastly increase in the next 5-10 years.

State of the Science: Psychotherapeutic Interventions for Prolonged Grief Disorder

Prolonged grief disorder (PGD) is a distinct diagnostic entity that has recently garnered considerable attention as it describes an intense, enduring, distressing and disabling bereavement reaction experienced by a small minority of community-based mourners. In recent decades, research has exploded to address how best to treat PGD with different psychotherapeutic interventions. In this state-of-the-science review, the strength of the evidence will be discussed regarding common psychotherapeutic interventions used to treat grief. Specifically, we focus on the most commonly used interventions, cognitive behavioral (CB)-based therapies, bereavement and support groups, and brief contact interventions (BCIs), in an effort to summarize the relevant clinical takeaways of the current available research. A discussion of the use of these therapies in specific clinical populations is also included, with a focus on those traumatically bereaved, pediatric populations, communities of color, and underserved communities. Important foci and directions for future research are also discussed.

Unexplained infertility and age-related infertility: indistinguishable diagnostic entities but different IVF prognosis.

Unexplained infertility and age-related infertility: indistinguishable diagnostic entities but different IVF prognosis.

Diagnostically distinct resting state fMRI energy distributions: A subject-specific maximum entropy modeling study.

Objective Existing neuroimaging studies of psychotic and mood disorders have reported brain activation differences (first-order properties) and altered pairwise correlation based functional connectivity (second-order properties). However, both approaches have certain limitations that can be overcome by integrating them in a pairwise maximum entropy model (MEM) that better represents a comprehensive picture of fMRI signal patterns and provides a system-wide summary measure called energy. This study examines the applicability of individual-level MEM for psychiatry and identifies image-derived model coefficients related to model parameters. Method MEMs are fit to resting state fMRI data from each individual with schizophrenia/schizoaffective disorder, bipolar disorder, and major depression (n=132) and demographically matched healthy controls (n=132) from the UK Biobank to different subsets of the default mode network (DMN) regions. Results The model satisfactorily explained observed brain energy state occurrence probabilities across all participants, and model parameters were significantly correlated with image-derived coefficients for all groups. Within clinical groups, averaged energy level distributions were higher in schizophrenia/schizoaffective disorder but lower in bipolar disorder compared to controls for both bilateral and unilateral DMN. Major depression energy distributions were higher compared to controls only in the right hemisphere DMN. Conclusions Diagnostically distinct energy states suggest that probability distributions of temporal changes in synchronously active nodes may underlie each diagnostic entity. Subject-specific MEMs allow for factoring in the individual variations compared to traditional group-level inferences, offering an improved measure of biologically meaningful correlates of brain activity that may have potential clinical utility.