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Towards Precision Medicine in Psychosis

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A special issue of Journal of Personalized Medicine (ISSN 2075-4426).

Deadline for manuscript submissions: closed (30 July 2022) | Viewed by 33060

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Prof. Dr. Seon-Cheol Park

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Department of Psychiatry, Hanyang University College of Medicine, Seoul 02841, Korea
Interests: psychopathology; network analysis; psychosis
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Dear Colleagues,

Precision medicine has been considered a promising diagnostic and therapeutic approach in psychiatry for the purpose of improving disease prevention, thereby increasing effectiveness and reducing adverse effects, based on the individual patient’s clinical and biological characteristics. Whereas traditional approaches have been based on a single clinical characteristic, precision medicine is based on an integration of clinical, molecular, genetic, neuroimaging, and other aspects in psychiatry. Since it has been reported that structural and functional brain abnormalities are related to the early stages of psychosis, it is estimated that these findings can contribute to the prediction of clinical onset and outcome. Furthermore, genetic, immunological, oxidative, metabolic, hormonal, dopaminergic, and other aspects have been considered major issues in terms of precision medicine with respect to psychosis. Despite its advancement, precision medicine in psychosis remains in the early phase, since there have been several limitations including a small sample size, low statistical power, lack of external validation for identified biomarkers, and others. This Special Issue of the Journal of Personalized Medicine aims to highlight the current scientific knowledge and reveal some of the latest findings in the field of precision medicine with respect to psychosis. Candidate biomarkers that are based on clinical, genetic, and neuroimaging approaches or combinations thereof may be investigated. The scientific advances in the field of precision medicine will continue to pave the way toward optimal recovery.

Prof. Dr. Seon-Cheol Park
Guest Editor

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Keywords

precision medicine
psychosis
biomarker
genetic
neuroimaging
integration

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Published Papers (9 papers)

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Research

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11 pages, 293 KiB

Open AccessArticle

Association between Peripheral Inflammatory Cytokines and Cognitive Function in Patients with First-Episode Schizophrenia

by Seon-Hwa Baek, Honey Kim, Ju-Wan Kim, Seunghyong Ryu, Ju-Yeon Lee, Jae-Min Kim, Il-Seon Shin and Sung-Wan Kim

J. Pers. Med. 2022, 12(7), 1137; https://doi.org/10.3390/jpm12071137 - 14 Jul 2022

Cited by 15 | Viewed by 2442

Abstract

In this study, we investigated the impact of inflammatory cytokines on the cognitive performance of patients with schizophrenia. The included patients met the criteria for schizophrenia spectrum disorder and were aged between 15 and 40 years, with a duration of illness ≤1 year. Plasma tumor necrosis factor (TNF)-α; interferon-γ; and interleukin (IL)-1β, IL-6, IL-8, IL-10, and IL-12 levels were measured. A computerized neurocognitive battery, measures for social cognitive function, and clinical measures were administered. A total of 174 patients with first-episode psychosis were enrolled. The TNF-α level was negatively correlated with scores on the digit span, verbal learning, and Wisconsin card sorting tests, and the number of correct responses on the continuous performance test (CR-CPT), whereas a positive correlation was detected with the trail making test (TMT)-B time. The interferon-γ level was negatively correlated with performance on the false belief and visual learning tests. The IL-1β level was positively correlated with the TMT-A time and CPT reaction time, whereas it was negatively correlated with the CR-CPT and performance on the visual learning and social cognitive tests. The IL-12 level was negatively correlated with the CR-CPT and false belief test. Our results suggest that proinflammatory cytokines are associated with cognitive impairment in patients with schizophrenia. Full article

(This article belongs to the Special Issue Towards Precision Medicine in Psychosis)

13 pages, 1660 KiB

Open AccessArticle

Psilocybin—Mediated Attenuation of Gamma Band Auditory Steady-State Responses (ASSR) Is Driven by the Intensity of Cognitive and Emotional Domains of Psychedelic Experience

by Vojtěch Viktorin, Inga Griškova-Bulanova, Aleksandras Voicikas, Dominika Dojčánová, Peter Zach, Anna Bravermanová, Veronika Andrashko, Filip Tylš, Jakub Korčák, Michaela Viktorinová, Vlastimil Koudelka, Kateřina Hájková, Martin Kuchař, Jiří Horáček, Martin Brunovský and Tomáš Páleníček

J. Pers. Med. 2022, 12(6), 1004; https://doi.org/10.3390/jpm12061004 - 19 Jun 2022

Cited by 5 | Viewed by 3846

Abstract

Psilocybin is a classical serotoninergic psychedelic that induces cognitive disruptions similar to psychosis. Gamma activity is affected in psychosis and is tightly related to cognitive processing. The 40 Hz auditory steady-state responses (ASSR) are frequently used as indicators to test the ability to generate gamma activity. Based on previous literature, we studied the impact of psilocybin on 40 Hz ASSR in healthy volunteers. The study was double blind and placebo controlled with a crossover design. A sample of 20 healthy subjects (10M/10F) received psilocybin orally 0.26 mg/kg or placebo. Participants were measured four times in total, one time before ingestion of psilocybin/placebo and one time after ingestion, during the peak of intoxication. A series of 500 ms click trains were used for stimulation. Psilocybin induced a psychedelic effect and decreased 40 Hz ASSR phase-locking index compared to placebo. The extent of the attenuation was related to Cognition and Affect on the Hallucinogen Rating Scale. The current study shows that psilocybin lowers the synchronization level and the amplitude of 40 Hz auditory steady-state responses, which yields further support for the role of gamma oscillations in cognitive processing and its disturbance. Full article

(This article belongs to the Special Issue Towards Precision Medicine in Psychosis)

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17 pages, 1679 KiB

Open AccessArticle

Aberrant Gamma-Band Oscillations in Mice with Vitamin D Deficiency: Implications on Schizophrenia and its Cognitive Symptoms

by Seungyeong Yu, Mincheol Park, Jiseung Kang, Eunkyung Lee, Jieun Jung and Tae Kim

J. Pers. Med. 2022, 12(2), 318; https://doi.org/10.3390/jpm12020318 - 20 Feb 2022

Cited by 4 | Viewed by 3754

Abstract

Vitamin D plays an essential role in cognitive functions as well as regulating calcium homeostasis and the immune system. Many epidemiological studies have also shown the close relationship between vitamin D deficiency (VDD) and the risk of schizophrenia. Cortical gamma-band oscillations (GBO) are associated with cognitive functions, such as attention and memory. Patients with schizophrenia show abnormal GBO with increased spontaneous GBO and decreased evoked GBO. However, the direct effect of VDD on GBO remains unknown. Parvalbumin interneurons, which predominantly contribute to the generation of GBO, are surrounded by perineuronal nets (PNN). We sought to investigate the associations among VDD, PNN, and GBO. Here, we injected a viral vector (AAV5-DIO-ChR2-eYFP) into the basal forebrain stereotaxically and implanted electrodes for electroencephalogram (EEG). At baseline, the evoked and spontaneous EEG power at the gamma frequency band was measured in 4-month-old male PV-Cre mice. After six and twenty weeks of vitamin D deficient food administration, the power of GBO was measured in the VDD condition. Next, we injected the chondroitinase ABC (ChABC) enzyme into the frontal cortex to eliminate PNN. We found that the VDD group showed decreased power of both optogenetically- and auditory-evoked GBO, whereas the spontaneous GBO increased. Enzymatic digestion of PNN showed similar changes in GBO. Taken together, we suggest that VDD could result in decreased PNN and, consequently, increase the spontaneous GBO and decrease the evoked GBO, reminiscent of the aberrant GBO in schizophrenia. These results show that VDD might increase the risk of schizophrenia and aggravate the cognitive symptoms of schizophrenia. Full article

(This article belongs to the Special Issue Towards Precision Medicine in Psychosis)

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12 pages, 278 KiB

Open AccessArticle

Low-Density Lipoprotein Cholesterol Is a Possible Blood Biomarker of Schizoid Personality Traits among Females

by Kohei Hayakawa, Motoki Watabe, Hideki Horikawa, Mina Sato-Kasai, Norihiro Shimokawa, Tomohiro Nakao and Takahiro A. Kato

J. Pers. Med. 2022, 12(2), 131; https://doi.org/10.3390/jpm12020131 - 19 Jan 2022

Cited by 2 | Viewed by 3373

Abstract

Lower serum levels of low-density lipoprotein cholesterol (LDL-C) have been suggested to indicate higher suicide risk and various psychiatric symptoms. Previously, we reported that lower serum LDL-C levels are associated with loneliness, social phobia, isolated life with little social support, and lower trust in others among young non-clinical females. Thus, we hypothesize that schizoid personality traits may be associated with lower serum LDL-C. We here verified this hypothesis using non-clinical data and clinical data with schizophrenia. Using the database from the Midlife in Japan (MIDJA), a cohort of residents living in Tokyo, we analyzed whether schizoid-related interpersonal characteristics were associated with LDL-C. In addition, we assessed the association between blood biomarkers including LDL-C and schizoid personality traits in 101 adult non-clinical volunteers. Finally, we evaluated the interaction between LDL-C and social decision making of patients with schizophrenia. In female non-clinical volunteers, serum LDL-C level was a predictive factor and negatively correlated with schizoid personality traits. Female patients with schizophrenia, whose serum LDL-C levels were lower, tended not to trust other females. The present findings suggest that LDL-C may influence schizoid personality traits in females, which provide a basis for further investigation into the biological aspects of schizoid personality disorder. Full article

(This article belongs to the Special Issue Towards Precision Medicine in Psychosis)

13 pages, 1406 KiB

Open AccessArticle

Network Analysis-Based Disentanglement of the Symptom Heterogeneity in Asian Patients with Schizophrenia: Findings from the Research on Asian Psychotropic Prescription Patterns for Antipsychotics

by Joonho Choi, Hyung-Jun Yoon, Jae Hong Park, Yukako Nakagami, Chika Kubota, Toshiya Inada, Takahiro A. Kato, Shu-Yu Yang, Sih-Ku Lin, Mian-Yoon Chong, Ajit Avasthi, Sandeep Grover, Roy Abraham Kallivayalil, Andi Jaylangkara Tanra, Kok Yoon Chee, Yu-Tao Xiang, Kang Sim, Afzal Javed, Chay Hoon Tan, Norman Sartorius, Shigenobu Kanba, Naotaka Shinfuku, Yong Chon Park and Seon-Cheol Park Show full author list Hide full author list

J. Pers. Med. 2022, 12(1), 33; https://doi.org/10.3390/jpm12010033 - 3 Jan 2022

Cited by 4 | Viewed by 2967

Abstract

The symptom heterogeneity of schizophrenia is consistent with Wittgenstein’s analogy of a language game. From the perspective of precision medicine, this study aimed to estimate the symptom presentation and identify the psychonectome in Asian patients, using data obtained from the Research on Asian Psychotropic Prescription Patterns for Antipsychotics. We constructed a network structure of the Brief Psychiatric Rating Scale (BPRS) items in 1438 Asian patients with schizophrenia. Furthermore, all the BPRS items were considered to be an ordered categorical variable ranging in value from 1–7. Motor retardation was situated most centrally within the BPRS network structure, followed by depressive mood and unusual thought content. Contrastingly, hallucinatory behavior was situated least centrally within the network structure. Using a community detection algorithm, the BPRS items were organized into positive, negative, and general symptom clusters. Overall, DSM symptoms were not more central than non-DSM symptoms within the symptom network of Asian patients with schizophrenia. Thus, motor retardation, which results from the unmet needs associated with current antipsychotic medications for schizophrenia, may be a tailored treatment target for Asian patients with schizophrenia. Based on these findings, targeting non-dopamine systems (glutamate, γ-aminobutyric acid) may represent an effective strategy with respect to precision medicine for psychosis. Full article

(This article belongs to the Special Issue Towards Precision Medicine in Psychosis)

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Review

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11 pages, 584 KiB

Open AccessReview

Epilepsy and Diagnostic Dilemmas: The Role of Language and Speech-Related Seizures

by Soultana Papadopoulou, Efterpi Pavlidou, Georgios Argyris, Thaleia Flouda, Panagiota Koukoutsidi, Konstantinos Krikonis, Sidrah Shah, Dana Chirosca-Vasileiou and Stergios Boussios

J. Pers. Med. 2022, 12(4), 647; https://doi.org/10.3390/jpm12040647 - 18 Apr 2022

Cited by 1 | Viewed by 4597

Abstract

Although the impact of epilepsy on expressive language is heavily discussed, researched, and scientifically grounded, a limited volume of research points in the opposite direction. What about the causal relationship between disorder-related language activities and epileptic seizures? What are the possible diagnostic dilemmas that experts in the field of speech-language pathology, neurology, and related fields face? How far has research gone in investigating psychogenic nonepileptic seizures, the misdiagnosis of which can be a thorny issue for clinicians and a detrimental factor for the patients’ health? In order to address these questions, the study at hand focuses on a common, ever-intensified (by the COVID-19 pandemic) speech disorder—stuttering, and explores the pathophysiological and psychogenic background of the phenomenon. It also looks at the role of stuttering as a contributing factor to the appearance of epileptic seizures, in the hope of drawing attention to the complexity and importance of precise detection of stuttering-induced epilepsy, as a specific subcategory of language-induced epilepsy. Full article

(This article belongs to the Special Issue Towards Precision Medicine in Psychosis)

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11 pages, 258 KiB

Open AccessReview

Clinical Approaches to Late-Onset Psychosis

by Kiwon Kim, Hong Jin Jeon, Woojae Myung, Seung Wan Suh, Su Jeong Seong, Jae Yeon Hwang, Je il Ryu and Seon-Cheol Park

J. Pers. Med. 2022, 12(3), 381; https://doi.org/10.3390/jpm12030381 - 2 Mar 2022

Cited by 5 | Viewed by 4527

Abstract

Psychosis can include schizophrenia, mood disorders with psychotic features, delusional disorder, active delirium, and neurodegenerative disorders accompanied by various psychotic symptoms. Late-onset psychosis requires careful intervention due to the greater associated risks of secondary psychosis; higher morbidity and mortality rates than early-onset psychosis; and complicated treatment considerations due to the higher incidence of adverse effects, even with the black box warning against antipsychotics. Pharmacological treatment, including antipsychotics, should be carefully initiated with the lowest dosage for short-term efficacy and monitoring of adverse side effects. Further research involving larger samples, more trials with different countries working in consortia, and unified operational definitions for diagnosis will help elaborate the clinical characteristics of late-onset psychosis and lead to the development of treatment approaches. Full article

(This article belongs to the Special Issue Towards Precision Medicine in Psychosis)

8 pages, 250 KiB

Open AccessReview

Implication of Electrophysiological Biomarkers in Psychosis: Focusing on Diagnosis and Treatment Response

by Ho Sung Lee and Ji Sun Kim

J. Pers. Med. 2022, 12(1), 31; https://doi.org/10.3390/jpm12010031 - 2 Jan 2022

Cited by 6 | Viewed by 2176

Abstract

Precision medicine has been considered a promising approach to diagnosis, treatment, and various interventions, considering the individual clinical and biological characteristics. Recent advances in biomarker development hold promise for guiding a new era of precision medicine style trials for psychiatric illnesses, including psychosis. Electroencephalography (EEG) can directly measure the full spatiotemporal dynamics of neural activation associated with a wide variety of cognitive processes. This manuscript reviews three aspects: prediction of diagnosis, prognostic aspects of disease progression and outcome, and prediction of treatment response that might be helpful in understanding the current status of electrophysiological biomarkers in precision medicine for patients with psychosis. Although previous EEG analysis could not be a powerful method for the diagnosis of psychiatric illness, recent methodological advances have shown the possibility of classifying and detecting mental illness. Some event-related potentials, such as mismatch negativity, have been associated with neurocognition, functioning, and illness progression in schizophrenia. Resting state studies, sophisticated ERP measures, and machine-learning approaches could make technical progress and provide important knowledge regarding neurophysiology, disease progression, and treatment response in patients with schizophrenia. Identifying potential biomarkers for the diagnosis and treatment response in schizophrenia is the first step towards precision medicine. Full article

(This article belongs to the Special Issue Towards Precision Medicine in Psychosis)

13 pages, 3598 KiB

Open AccessFeature PaperReview

Psychosis in Women: Time for Personalized Treatment

by Marianna Mazza, Emanuele Caroppo, Domenico De Berardis, Giuseppe Marano, Carla Avallone, Georgios D. Kotzalidis, Delfina Janiri, Lorenzo Moccia, Alessio Simonetti, Eliana Conte, Giovanni Martinotti, Luigi Janiri and Gabriele Sani

J. Pers. Med. 2021, 11(12), 1279; https://doi.org/10.3390/jpm11121279 - 2 Dec 2021

Cited by 27 | Viewed by 4073

Abstract

Early detection and prompt treatment of psychosis is of the utmost importance. The great variability in clinical onset, illness course, and response to pharmacological and psychosocial treatment is in great part gender-related. Our aim has been to review narratively the literature focusing on gender related differences in the psychoses, i.e., schizophrenia spectrum disorders. We searched the PubMed/Medline, Scopus, Embase, and ScienceDirect databases on 31 July 2021, focusing on recent research regarding sex differences in early psychosis. Although women, compared to men, tend to have better overall functioning at psychotic symptom onset, they often present with more mood symptoms, may undergo misdiagnosis and delay in treatment and are at a higher risk for antipsychotic drug-induced metabolic and endocrine-induced side effects. Furthermore, women with schizophrenia spectrum disorders have more than double the odds of having physical comorbidities than men. Tailored treatment plans delivered by healthcare services should consider gender differences in patients with a diagnosis of psychosis, with a particular attention to early phases of disease in the context of the staging model of psychosis onset. Full article

(This article belongs to the Special Issue Towards Precision Medicine in Psychosis)

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