Since the origins of psychiatry, mental health has been considered a manifestation of brain pathology. Kraepelin described schizophrenia as early-onset dementia, believing the disease originated from a structural brain anomaly. During the 20th century, efforts were made toward finding anatomopathological evidence on post-mortem mental health patients, with no success . The lack of findings caused a loss of interest; still, the eagerness to find the etiology of the psychiatric symptoms persisted, especially when treatments like malaria therapy, cardiozolic and electro-convulsive therapies, insulin comas, and the first psychiatric medications showed clinical improvements .
In 1976, with the development of Computerized tomography (CT), in vivo visualization of the brain was possible, and lateral ventricle enlargement was documented in patients with schizophrenia (SS). In 1980, Dr. Timothy Crow characterized two types of schizophrenia differenced by clinical aspects, exacerbation with amphetamines, response to antipsychotics, and size of their lateral ventricles on CT . In 1986, Daniel Weinberger studied brain blood flow with inhaled Xenon 133. He discovered that SS did not elevate their frontal lobe flow during complex cognitive tasks, different from healthy subjects (CS) , and named it hypo-frontality, calling back the attention to psychiatric functional neuro-imaging to elucidate the origin of psychiatric symptoms.
Functional studies with PET and SPET brought the possibility of measuring glucose metabolism, the brain's blood flow, its distribution, receptor activities, and levels of enzymes and neurotransmitters [5–6]. Nonetheless, the need for radioligands created the urge to reduce radiation without affecting the anatomical, dynamical, functional, and metabolic aspects .
Functional Magnetic Resonance Imaging (fMRI) generated the desire to relate functional brain abnormalities with the psychiatric diagnosis. Until now, it has been impossible to determine biomarkers that characterize mental pathologies allowing, through brain imaging, the adequate characterization of the disease, prognosis, the best treatment, and outcomes [5, 7]. The correlation between mental illness and imaging could impact the clinical aspects, aiding in developing an approach strategy that shifts the focus away from the nosological systems (which are categorical and limit the evaluation of the patient). Previous studies have been heterogenic due to differences in psychiatric and psychopathology concepts, as in the methodologies (inclusion criteria, sociodemographic variables, experimental designs, forms of imaging acquisition, processing, and analysis).
The mental disease´s complexity was considered a consequence of the biological and environmental influence, genetics, and epigenetics of multiple systems levels . The evaluation of the behavior (cognition, emotions, social interactions, learning, motivation, and perception) are the visible "tips of the iceberg" when discussing the multiple levels' complexity. However, brain circuits may be the phenotypical expression of the cellular and subcellular, structural and functional, and genetic and epigenetic phenomena. Neural networks, their activation and deactivation processes, and their quantification are crucial elements in understanding the association between the brain and mental illness .
The fMRI aids in understanding how mental diseases relate to telencephalic circuits ; as such, it is primordial to associate them with the subjacent neuronal network . It has been proposed to redefine them in the dimension of observable behavior, which is aligned with the brain's biology. The NIH considered this and named it the RDoC (Research Domain Criteria) [12–13].
A practical way to mitigate methodological discrepancies in previous studies is by using fMRI [5–7]. The investigation based on symptomatic domains (SD) reflects the characteristics of the circuits and the behavior with an individualized approach, which concord with the singularity of the pathology [8–9, 11]. The DSM-5 proposes to move forward on the dimensional diagnosis stating that using imaging studies, the diagnostic approach should be agnostic about the current nosologic categories of the diseases , in favor of creating a correlation between psychopathologic manifestations and structural and functional findings. Following this, the proposed plan is to stop addressing the pathology from the definition and towards the neurobiological bases; but to approach the patient from the clinical aspects and the brain-behavior relationships, considering the relevance of the brain circuits. Multiple analysis elements must be employed, like images, behavior, and symptoms self-reports [2, 14]. The manuscript describes the spectrum of psychopathological symptoms in SS through correlations of the imaging findings on fMRI and the SD obtained with the SCL-90-R.