Heterogeneous trajectories in schizophrenia: insights from neurodevelopment and neuroprogression models

The notion that schizophrenia is a neuroprogressive disorder is based on clinical perception of cumulative impairments over time and is supported by neuroimaging and biomarker research. Nevertheless, increasing evidence has indicated that schizophrenia first emerges as a neurodevelopmental disorder that could follow various pathways, some of them neuroprogressive. The objective of this review is to revisit basic research on cognitive processes and neuroimaging findings in a search for candidate keys to the intricate connections between neurodevelopment and neuroprogression in schizophrenia. In the complete panorama, schizophrenia is a neurodevelopmental disorder, possibly associated with an additional burden over the course of the disease through pathologically accelerated aging, and cognitive heterogeneity may explain the different trajectories of each patient.

Neuroprogression in post-traumatic stress disorder: a systematic review

Abstract Introduction Neuroprogression has been proposed as the pathological rewiring of the brain that takes place in parallel with clinical and neurocognitive deterioration in the course of psychiatric disorders. This study aims to review the biological underpinnings and clinical outcomes related to neuroprogression in post-traumatic stress disorder (PTSD). Methods We performed a systematic review by searching PubMed, Embase, and Web of Science for articles published between January 1, 1960, and January 6, 2020. Inclusion criteria were met when articles assessed brain changes, neurocognition, functioning, inflammation, oxidative stress, and neurotrophins in patients with PTSD. Narrative review articles, case reports, and preclinical studies were excluded. Results A total of 965 abstracts were identified and 15 articles were included in our systematic review. It seems that for a subset of patients whose symptoms worsen or are maintained at a high intensity there is a progressive change in the frontal lobe, especially the prefrontal cortex, and worsening of both neurocognition (verbal memory and facial recognition) and functioning (physical, psychological, social and environmental). Conclusion Although current findings associate progressive reduction in frontal lobe size with neurocognitive impairment, further research is needed to characterize PTSD as a neuroprogressive disorder.

Cognitive impairment in bipolar disorder Neuroprogression or behavioral variant frontotemporal dementia? / Comprometimento cognitivo no transtorno bipolar: neuroprogressão ou variante comportamental da demência frontotemporal?

ABSTRACT Patients with Bipolar Disorder (BD) usually display cognitive deficits with aging. However, the correlation between BD and dementia syndromes is inconclusive, despite the similarity with behavioral variant frontotemporal dementia. We report a 78-year-old female patient who had bipolar type 1 disorder since adolescence. Her symptoms ranged from apathy to psychotic mania. She had had three hospitalizations, and since her last stay 10 years ago, her symptoms had remained stable. However, in the past 2 years, she displayed different symptoms, such as irritability manifested as verbal and physical aggression, cognitive impairment, repetitive pattern of behavior, perambulation, persecutory delusions, disorientation, and hyporexia. Treatment with anticholinesterases or mood stabilizers promoted no improvement. She scored 17/30 points on the Mini-Mental State Examination. Neuropsychological assessment suggested deficits in executive function, attention, and memory. Neuroimaging tests revealed frontotemporal degeneration and hypoperfusion. Diagnostic and therapeutic approaches for this type of patient represent a significant challenge for clinicians.

RESUMO Pacientes com Transtorno Bipolar (TB) costumam apresentardéficits cognitivosao envelhecer. No entanto, a correlação com síndromes demenciais é inconclusiva, apesar da similaridade com a variante comportamental da demência frontotemporal (bvFTD). Nósrelatamos uma paciente de 78 anos de idade com TB tipo 1 desde a adolescência. Seus sintomas variavam de apatia a mania psicótica. A paciente passou por 3 internações, sendo a última há 10 anos, seguida de estabilização clínica. No entanto, nos últimos 2 anos, ela apresentou sintomas diferentes, como irritabilidade expressada por agressões verbal e física, comprometimento cognitivo, padrão repetitivo de comportamento, perambulação, delírios persecutórios, desorientação e hiporexia. O tratamento com anticolinesterásicos ou estabilizadores de humor não revelou melhora. Apresentou 17/30 pontos no miniexame do estado mental, a avaliação neuropsicológica sugeriu déficit de função executiva, atenção e memória. Os exames de neuroimagem demonstraram atrofia e hipoperfusão fronto-temporal. Abordagens diagnósticas e terapêuticas para este tipo de paciente representam um desafio significativo para os clínicos.

The Staging of Major Mood Disorders: Clinical and Neurobiological Correlates

OBJECTIVE: Staging of psychiatric disorders is gaining momentum and the purpose of this review is to examine whether major mood disorders can be defined according to stages. METHODS: In April 2018 the PubMed electronic data base was scrutinized by a combination of various search terms like “major depressive disorder and staging,”“bipolar disorder and neuroprogression,” etc. To incorporate the latest findings the search was limited to the last 10 years. Both original and review articles were examined by reading the abstracts, and papers which were found to be particularly applicable were read in full and their reference lists were also consulted. RESULTS: A significant increase occurred in the number of papers published on the topic of staging of mood disorders. Staging formats were found for both major mood disorders, with the caveat that many more articles were discovered for bipolar disorder. Current evidence points to allostatic load and neuroprogression as the basis for staging of mood disorders. CONCLUSION: Principal affective illnesses may be characterized by distinct stages, for instance early, intermediate and late. These phases inform the management so that clinicians should incorporate the staging schema into everyday practice and implement treatment strategies according to the phase of the illness.

Staging Models in Bipolar Disorder: A Systematic Review of the Literature

Bipolar disorder is manifested as severe dysregulation of mood with recurrent manic and major depressive episodes. It is associated with psychiatric and medical comorbidities, inadequate response to currently available pharmacological agents and a progressively deteriorating course in many patients. The index episode is often depressive in nature, while the first manic or hypomanic episode may occur several years later in the course of the disorder causing delay in diagnosis and use of inappropriate treatment strategies. Staging has been used to great advantage in other branches of medicine like cardiology and oncology. There is growing realization that major mental disorders are fundamentally progressive, with simpler treatment requirements and better prognosis during initial stages of the illness. Defining these conditions into clinically applicable stages not only helps in better understanding the trajectory of a particular disorder, but also assists in management. Patients with a chronic, recalcitrant condition like bipolar disorder are likely to greatly benefit from this approach. If the illness is correctly identified early in its course, proper treatment can be instigated arresting progression to latter phases which are associated with myriad complications in the biopsychosocial realm. With these considerations, a search of the MEDLINE data base was conducted to seek out literature pertaining to staging models in bipolar disorder. A thorough scrutiny of the existing research work revealed that a number of investigators have endeavored to stage define bipolar disorder. This paper outlines staging proposals for bipolar disorder which have the greatest supporting evidence in the literature.

Staging and neuroprogression in bipolar disorder: a systematic review of the literature

INTRODUCTION: The use of clinical staging models is emerging as a novel and useful paradigm for diagnosing severe mental disorders. The term "neuroprogression" has been used to define the pathological reorganization of the central nervous system along the course of severe mental disorders. In bipolar disorder (BD), neural substrate reactivity is changed by repeated mood episodes, promoting a brain rewiring that leads to an increased vulnerability to life stress. METHOD: A search in the PubMed database was performed with the following terms: "staging", "neuroprogression", "serum", "plasma", "blood", "neuroimaging", "PET scan", "fMRI", "neurotrophins", "inflammatory markers" and "oxidative stress markers", which were individually crossed with "cognition", "functionality", "response to treatments" and "bipolar disorder". The inclusion criteria comprised original papers in the English language. Abstracts from scientific meetings were not included. RESULTS: We divided the results according to the available evidence of serum biomarkers as potential mediators of neuroprogression, with brain imaging, cognition, functioning and response to treatments considered as consequences. CONCLUSION: The challenge in BD treatment is translating the knowledge of neuronal plasticity and neurobiology into clinical practice. Neuroprogression and staging can have important clinical implications, given that early and late stages of the disorder appear to present different biological features and therefore may require different treatment strategies.