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Translational Psychiatry Jun 2024There is a lack of knowledge regarding the relationship between proneness to dimensional psychopathological syndromes and the underlying pathogenesis across major...
There is a lack of knowledge regarding the relationship between proneness to dimensional psychopathological syndromes and the underlying pathogenesis across major psychiatric disorders, i.e., Major Depressive Disorder (MDD), Bipolar Disorder (BD), Schizoaffective Disorder (SZA), and Schizophrenia (SZ). Lifetime psychopathology was assessed using the OPerational CRITeria (OPCRIT) system in 1,038 patients meeting DSM-IV-TR criteria for MDD, BD, SZ, or SZA. The cohort was split into two samples for exploratory and confirmatory factor analyses. All patients were scanned with 3-T MRI, and data was analyzed with the CAT-12 toolbox in SPM12. Psychopathological factor scores were correlated with gray matter volume (GMV) and cortical thickness (CT). Finally, factor scores were used for exploratory genetic analyses including genome-wide association studies (GWAS) and polygenic risk score (PRS) association analyses. Three factors (paranoid-hallucinatory syndrome, PHS; mania, MA; depression, DEP) were identified and cross-validated. PHS was negatively correlated with four GMV clusters comprising parts of the hippocampus, amygdala, angular, middle occipital, and middle frontal gyri. PHS was also negatively associated with the bilateral superior temporal, left parietal operculum, and right angular gyrus CT. No significant brain correlates were observed for the two other psychopathological factors. We identified genome-wide significant associations for MA and DEP. PRS for MDD and SZ showed a positive effect on PHS, while PRS for BD showed a positive effect on all three factors. This study investigated the relationship of lifetime psychopathological factors and brain morphometric and genetic markers. Results highlight the need for dimensional approaches, overcoming the limitations of the current psychiatric nosology.
Topics: Humans; Male; Female; Adult; Magnetic Resonance Imaging; Bipolar Disorder; Depressive Disorder, Major; Schizophrenia; Psychotic Disorders; Gray Matter; Middle Aged; Genome-Wide Association Study; Factor Analysis, Statistical; Brain; Psychopathology; Multifactorial Inheritance; Cerebral Cortex
PubMed: 38830892
DOI: 10.1038/s41398-024-02936-6 -
Cureus Apr 2024Semaglutide (Ozempic), a GLP-1 receptor agonist effective in weight management, and ziprasidone (Geodon), an antipsychotic with a lower risk of metabolic side effects,...
Semaglutide (Ozempic), a GLP-1 receptor agonist effective in weight management, and ziprasidone (Geodon), an antipsychotic with a lower risk of metabolic side effects, are well-established in treating type 2 diabetes and schizophrenia, respectively. However, their interactions and effects on psychiatric symptoms are less understood. In this study, we report a case of a 43-year-old male with schizophrenia and diabetes with exacerbated paranoid delusions upon semaglutide administration for weight loss; symptoms peaked at higher doses and subsided after dose reduction. Concurrently, serum ziprasidone levels were significantly elevated at the dose reduction, suggesting a pharmacokinetic interaction likely due to semaglutide-induced slowed gastric emptying affecting ziprasidone's absorption and metabolism. This study illustrates the need for careful monitoring of psychiatric symptoms and drug levels when these medications are used together. Additionally, further research into their interactions to optimize treatment for patients with coexisting metabolic and psychiatric conditions is warranted.
PubMed: 38817502
DOI: 10.7759/cureus.59319 -
Alpha Psychiatry Jan 2024Schizophrenia patients often have personality disorders; schizophrenia patients with personality disorders are more difficult to treat and have a worse prognosis. Early...
OBJECTIVE
Schizophrenia patients often have personality disorders; schizophrenia patients with personality disorders are more difficult to treat and have a worse prognosis. Early identification of this group of patients and early intervention can achieve better prognosis. Therefore, it is very important to explore effective biomarkers and early diagnosis for the prognosis of schizophrenia. The primary purpose of this paper is to explore the relationship between plasma miRNA expression level and personality disorder with schizophrenia.
METHODS
Gene microarrays in miRNA files were employed, and the plasma of peripheral blood of 82 schizophrenic patients and 43 healthy control subjects were examined. Real-time reverse transcription polymerase chain reaction detection were performed to explore the results. Spearman correlation analysis was used to analyze the correlation between expression level of miRNAs and Personality Diagnosis Questionnaire-4 score.
RESULTS
The results showed that miR-1273d, miR-1303, miR-3064-5p, miR-3131, miR-3687, miR-4428, miR-4725-3p, and miR-5096 were up-regulated in schizophrenic patients. Compared to healthy control subjects, the difference was statistically significant ( < .05). Schizophrenic patients with schizoid, paranoid, schizotypal, and obsessive compulsive traits had negative correlation with miR-1303, miR-3131, miR-4428, and miR-5096 expression level ( = -0.40 to -0.62, < .05); there were no significant differences in the other miRNAs. Correlation with other personality traits was not significant ( > .05). The stepwise regression analysis indicated that miR-5096, miR-3131, and miR-1273d have a significant predictive effect on the schizoid trait ( < .01). MiR-4428 and miR-1303 had a significant predictive effect on the schizotypal trait ( < .01). MiR-5096, miR-4428, and miR-4725-3P had a significant predictive effect on the paranoid trait ( < .05). MiR-4428, miR-1303, and miR-5096 had a significant predictive effect on the obsessive compulsive trait ( < .05).
CONCLUSION
The expression levels of miR-1273d, miR-1303, miR-3064-5p, miR-3131, miR-3687, miR-4428, miR-4725-3p, and miR-5096 were up-regulated in the peripheral blood of patients with schizophrenia, and these miRNAs are expected to be diagnostic biomarkers for accurate diagnosis of schizophrenia. The expression levels of miR-1303, miR-3131, miR-1273d, miR-4428, miR-4725-3p, and miR-5096 have significant predictive effects on personality disorder in schizophrenia.
PubMed: 38799488
DOI: 10.5152/alphapsychiatry.2024.231216 -
Brain Sciences May 2024Theory of Mind (ToM) impairment has repeatedly been found in paranoid schizophrenia. The current study aims at investigating whether this is related to a deficit in ToM...
BACKGROUND
Theory of Mind (ToM) impairment has repeatedly been found in paranoid schizophrenia. The current study aims at investigating whether this is related to a deficit in ToM (undermentalizing) or an increased ToM ability to hyperattribute others' mental states (overmentalizing).
METHODS
Mental state attribution was examined in 24 patients diagnosed with schizophrenia (12 acute paranoid (APS) and 12 post-acute paranoid (PPS)) with regard to positive symptoms as well as matched healthy persons using a moving shapes paradigm. We used 3-T-functional magnetic resonance imaging (fMRI) to provide insights into the neural underpinnings of ToM due to attributional processes in different states of paranoid schizophrenia.
RESULTS
In the condition that makes demands on theory of mind skills (ToM condition), in patients with diagnosed schizophrenia less appropriate mental state descriptions have been used, and they attributed mental states less often to the moving shapes than healthy persons. On a neural level, patients suffering from schizophrenia exhibited within the ToM network hypoactivity in the medial prefrontal cortex (MPFC) and hyperactivity in the temporo-parietal junction (TPJ) as compared to the healthy sample.
CONCLUSIONS
Our results indicate both undermentalizing and hypoactivity in the MPFC and increased overattribution related to hyperactivity in the TPJ in paranoid schizophrenia, providing new implications for understanding ToM in paranoid schizophrenia.
PubMed: 38790440
DOI: 10.3390/brainsci14050461 -
Frontiers in Psychiatry 2024Impaired function of brain morphogenic genes is considered one of the predisposing factors for the manifestation of psychiatric and cognitive disorders, such as paranoid...
INTRODUCTION
Impaired function of brain morphogenic genes is considered one of the predisposing factors for the manifestation of psychiatric and cognitive disorders, such as paranoid schizophrenia (SCZ) and major depressive disorder (MDD). Identification of such genes (genes of neurotrophic factors and guidance molecules among them) and their deleterious genetic variants serves as a key to diagnosis, prevention, and possibly treatment of such disorders. In this study, we have examined the prevalence of genomic variants in brain morphogenic genes in individuals with SCZ and MDD within a Russian population.
METHODS
We have performed whole-exome sequencing of 21 DNA samples: 11 from individuals with SCZ and 10 with MDD, followed by ARMS (Amplification-Refractory Mutation System) based screening of detected single nucleotide variants (SNVs) in larger groups: 102 for individuals with SCZ, 79 for those with MDD and 103 for healthy donors.
RESULTS
Whole-exome sequencing has revealed 226 missense mutations in 79 genes (out of 140 studied), some of which occur in patients with psychiatric disorders significantly more frequently than in healthy donors. We have identified previously undescribed genomic variants in brain morphogenic genes: (rs1944294-T and rs17445840-T), (rs11935573-G and rs12500437-G/T) and (rs1227051-G/A), significantly associated with the incidence of SCZ and MDD in the Russian population. For some SNVs (rs6265-T, rs1944294-T, rs11935573-G, rs4760-G) sex-biased differences in their prevalence between SCZ/MDD patients and healthy donors was detected.
DISCUSSION
However, the functional significance of the SNVs identified has still to be confirmed in cellular and animal models. Once it is fulfilled, these SNVs have the potential to complement the diagnostic toolbox for assessing susceptibility to mental disorders. The data obtained indirectly confirm the importance of adequate brain structure formation for its correct functioning and preservation of mental health.
PubMed: 38699454
DOI: 10.3389/fpsyt.2024.1338168 -
Cureus Mar 2024Schizophrenia affects 1% of the population, causing chronic debilitating symptoms with largely unknown causes. Structural brain changes and neurochemical alterations are...
Schizophrenia affects 1% of the population, causing chronic debilitating symptoms with largely unknown causes. Structural brain changes and neurochemical alterations are believed to contribute to its etiology. Delayed treatment initiation is a major concern. This case involves a male patient with a decade-long history of psychosis, experiencing isolation, agoraphobia, and paranoid delusions. His situation deteriorated to the point where he lived in a self-imposed physically constraining environment for a year, leading to muscle atrophy and deteriorating health. Delayed help-seeking was driven by insurance concerns, despite prior academic success. Following extensive evaluation, he received the diagnosis of schizophrenia (first episode, severe), requiring multidisciplinary treatment, including medication adjustments and therapy. This case serves as a poignant illustration of a missed opportunity for early intervention, with treatment initiated only after symptoms became severe. Research indicates that early intervention in schizophrenia is crucial, typically leading to improved outcomes, emphasizing its critical importance.
PubMed: 38681378
DOI: 10.7759/cureus.57191 -
Cureus Mar 2024Assessing patient decision-making capacity while adhering to the requests of patients with mental illness remains a great ethical challenge. In patients with severe...
Assessing patient decision-making capacity while adhering to the requests of patients with mental illness remains a great ethical challenge. In patients with severe mental illness, the assessment of decision-making capacity can be difficult, particularly when a care team is also trying to navigate cultural, educational, and linguistic barriers. It becomes especially complex in situations where the patient is not only diagnosed with a severe mental illness but also suffers from a comorbid medical illness that the patient refuses to have treated appropriately. Balancing patient wishes while respecting patient autonomy creates further issues when assessing decision-making capacity. As such, the following case presents a transgender man who suffers from schizophrenia with a persistent skin infection on the patient's torso secondary to wearing a brassiere for an extended period. This case report addresses the intricacies surrounding patient decision-making capacity, specifically in the psychiatric population.
PubMed: 38681311
DOI: 10.7759/cureus.57123 -
Visualizing threat and trustworthiness prior beliefs in face perception in high versus low paranoia.Schizophrenia (Heidelberg, Germany) Mar 2024Predictive processing accounts of psychosis conceptualize delusions as overly strong learned expectations (prior beliefs) that shape cognition and perception. Paranoia,...
Predictive processing accounts of psychosis conceptualize delusions as overly strong learned expectations (prior beliefs) that shape cognition and perception. Paranoia, the most prevalent form of delusions, involves threat prior beliefs that are inherently social. Here, we investigated whether paranoia is related to overly strong threat prior beliefs in face perception. Participants with subclinical levels of high (n = 109) versus low (n = 111) paranoia viewed face stimuli paired with written descriptions of threatening versus trustworthy behaviors, thereby activating their threat versus trustworthiness prior beliefs. Subsequently, they completed an established social-psychological reverse correlation image classification (RCIC) paradigm. This paradigm used participants' responses to randomly varying face stimuli to generate individual classification images (ICIs) that intend to visualize either facial prior belief (threat vs. trust). An independent sample (n = 76) rated these ICIs as more threatening in the threat compared to the trust condition, validating the causal effect of prior beliefs on face perception. Contrary to expectations derived from predictive processing accounts, there was no evidence for a main effect of paranoia. This finding suggests that paranoia was not related to stronger threat prior beliefs that directly affected face perception, challenging the assumption that paranoid beliefs operate on a perceptual level.
PubMed: 38509135
DOI: 10.1038/s41537-024-00459-z