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Pharmacology Research & Perspectives Aug 2024It is a paradox that psychotomimetic drugs can relieve symptoms that increase risk of and cooccur with psychosis, such as attention and motivational deficits (e.g.,... (Review)
Review
It is a paradox that psychotomimetic drugs can relieve symptoms that increase risk of and cooccur with psychosis, such as attention and motivational deficits (e.g., amphetamines), pain (e.g., cannabis) and symptoms of depression (e.g., psychedelics, dissociatives). We introduce the ideas of psychotomimetic compensation and psychotomimetic sensitization to explain this paradox. Psychotomimetic compensation refers to a short-term stressor or drug-induced compensation against stress that is facilitated by engagement of neurotransmitter/modulator systems (endocannabinoid, serotonergic, glutamatergic and dopaminergic) that mediate the effects of common psychotomimetic drugs. Psychotomimetic sensitization occurs after repeated exposure to stress and/or drugs and is evidenced by the gradual intensification and increase of psychotic-like experiences over time. Theoretical and practical implications of this model are discussed.
Topics: Humans; Hallucinogens; Animals; Stress, Psychological; Psychoses, Substance-Induced; Neurotransmitter Agents
PubMed: 38923845
DOI: 10.1002/prp2.1217 -
Psychiatry and Clinical Neurosciences Jun 2024Schizophrenia (SZ) is a brain disorder characterized by psychotic symptoms and cognitive dysfunction. Recently, irregularities in sharp-wave ripples (SPW-Rs) have been...
AIMS
Schizophrenia (SZ) is a brain disorder characterized by psychotic symptoms and cognitive dysfunction. Recently, irregularities in sharp-wave ripples (SPW-Rs) have been reported in SZ. As SPW-Rs play a critical role in memory, their irregularities can cause psychotic symptoms and cognitive dysfunction in patients with SZ. In this study, we investigated the SPW-Rs in human SZ.
METHODS
We measured whole-brain activity using magnetoencephalography (MEG) in patients with SZ (n = 20) and sex- and age-matched healthy participants (n = 20) during open-eye rest. We identified SPW-Rs and analyzed their occurrence and time-frequency traits. Furthermore, we developed a novel multivariate analysis method, termed "ripple-gedMEG" to extract the global features of SPW-Rs. We also examined the association between SPW-Rs and brain state transitions. The outcomes of these analyses were modeled to predict the positive and negative syndrome scale (PANSS) scores of SZ.
RESULTS
We found that SPW-Rs in the SZ (1) occurred more frequently, (2) the delay of the coupling phase (3) appeared in different brain areas, (4) consisted of a less organized spatiotemporal pattern, and (5) were less involved in brain state transitions. Finally, some of the neural features associated with the SPW-Rs were found to be PANSS-positive, a pathological indicator of SZ. These results suggest that widespread but disorganized SPW-Rs underlies the symptoms of SZ.
CONCLUSION
We identified irregularities in SPW-Rs in SZ and confirmed that their alternations were strongly associated with SZ neuropathology. These results suggest a new direction for human SZ research.
PubMed: 38923051
DOI: 10.1111/pcn.13702 -
Acta Psychiatrica Scandinavica Jun 2024Anticipating diagnostic change from major depressive (MDD) to bipolar disorder (BD) can support better prognosis and treatment, especially of depression but is...
BACKGROUND
Anticipating diagnostic change from major depressive (MDD) to bipolar disorder (BD) can support better prognosis and treatment, especially of depression but is challenging and reported research results are inconsistent. We therefore assessed clinical characteristics associated with diagnostic change from MDD to BD with antidepressant treatments.
METHODS
We compared characteristics of 3212 initially MDD patients who became (hypo)manic during antidepressant treatment to those with stable MDD diagnoses as well as with cases of stable, spontaneous BD, using standard bivariate and multivariate statistics.
RESULTS
Among MDD patients, 6.69% [CI: 5.85-7.61] changed to BD, mostly type II (BD2, 76.7%). BD-converters had higher rates of familial mood disorders (74.1% vs. 57.1%) or BD (33.7% vs. 21.0%) and 2.8-years younger onset than stable MDD patients. They also had more prior depressive recurrences/year, years-of-illness, mood-stabilizer treatment, divorces, fewer children, more suicide attempts and drug-abuse, and higher intake cyclothymia, YMRS and MDQ scores. Predictors independently associated with diagnostic conversion were: more familial BD, depressions/year, unemployment, cyclothymic temperament, suicidal ideation or acts, and fewer children. BD-converters vs. spontaneous BD cases had significantly more suicide attempts, BD2 diagnoses, and affected relatives. Converting to vs. spontaneous BD1 was associated with more ADHD, more suicidal ideation or behavior, MDI course, and younger onset; converting to vs. spontaneous BD2 had more episodes/year, unemployment, ADHD, substance abuse, suicidal ideation or attempts, and more relatives with BD.
CONCLUSIONS
Few (6.69%) initially MDD subjects converted to BD, most (76.7%) to BD2. Independent predictive associations with diagnostic change included: familial BD, more depressions/year, unemployment, cyclothymic temperament, suicidal behavior and fewer children. Notably, several characteristics were stronger among those changing to BD during antidepressant treatment vs. others with spontaneous BD.
PubMed: 38922810
DOI: 10.1111/acps.13721 -
Behavioral Sciences (Basel, Switzerland) Jun 2024Improving social functioning deficits-a core characteristic of schizophrenia-spectrum disorders-is often listed by patients as a key recovery goal. Evidence suggests...
Improving social functioning deficits-a core characteristic of schizophrenia-spectrum disorders-is often listed by patients as a key recovery goal. Evidence suggests that social deficits also extend to people with schizotypy, a group at heightened risk for psychotic and other psychopathological disorders. One challenge of social functioning research in schizotypy is understanding whether social deficits arise from receiving less pleasure from social activities or from participating less in high-pleasure activities. However, limited information exists on what constitutes highly pleasurable, common social activities. In this study, 357 college students rated the frequency and enjoyment of 38 social activities. Our aims were to categorize activities based on their frequency and enjoyment, and whether these correlated with validated social functioning and schizotypy measures. We found that social activities could be characterized based on their frequency and enjoyment and created a frequency-enjoyment matrix that could be useful for future studies. Activities were correlated with social functioning, generally reaching a small effect size level, with increasing frequency and enjoyment showing associations with greater social functioning. Further, negative and disorganized-but not positive-traits were associated with less engagement and pleasure. Although follow-up studies in community samples are needed, our findings have the potential to help researchers and clinicians better understand which activities participants are more likely to engage in and derive pleasure from. The findings may also illustrate the extent to which social deficits may be due to less engagement or less pleasure from social activities, as well as which aspects of schizophrenia-spectrum disorders are associated with these facets of social functioning.
PubMed: 38920806
DOI: 10.3390/bs14060474 -
Frontiers in Psychology 2024Metacognitive Training (MCT) is widely used and effective in reducing positive symptoms in psychosis. Physical exercise, such as Water Aerobics (WA), improves general...
Efficacy of the combination of water aerobics and metacognitive training on psychological and physical health variables and their relationship with SP1 and SP4 biomarkers in people with psychosis: a study protocol.
BACKGROUND
Metacognitive Training (MCT) is widely used and effective in reducing positive symptoms in psychosis. Physical exercise, such as Water Aerobics (WA), improves general health, quality of life and symptoms as a low impact activity that allows social interactions. Preliminary results suggest a relationship between dopamine and psychotic symptoms, through SP transcription factors, SP1 and SP4 biomarkers. The aims of the project are to evaluate the efficacy of a combined intervention (WA and MCT) for psychosis to improve psychotic symptoms, physical health, and transcription levels of SP biomarkers.
MATERIALS AND METHODS
This is a unicentric randomized controlled trial of three parallel intervention groups: MCT, WA and combined intervention. The estimated sample will be 48 patients with a psychotic spectrum disorder diagnosis. The assessment will be performed at baseline and at 2-months' follow-up. Instruments used in the assessment will include clinical, cognitive, metacognitive, social cognitive and psychosocial variables.
DISCUSSION
This will be the first study investigating the impact of the combination of MCT and WA in psychosis. Moreover, it will be the first study analyzing changes in the transcriptional biomarkers SP1 and SP4 after interventions. The results of this study may have clinical implications contributing to the improvement of treatment selection.
CLINICAL TRIAL REGISTRATION
https://clinicaltrials.gov/, identifier: NCT05455593.
PubMed: 38919799
DOI: 10.3389/fpsyg.2024.1360004 -
Immunity & Ageing : I & A Jun 2024Neutrophils play an essential role in Alzheimer's disease (AD) pathology. However, the extent of their heterogeneity remains poorly explored, particularly in the context...
BACKGROUND
Neutrophils play an essential role in Alzheimer's disease (AD) pathology. However, the extent of their heterogeneity remains poorly explored, particularly in the context of developing novel therapies targeting these cells.
RESULTS
We investigate the population structure of neutrophils purified from peripheral blood samples of AD mice. Utilizing single cell RNA sequencing, we comprehensively map neutrophil populations into six distinct clusters and find that the Neu-5 subset is specially enriched in AD mice. This subset exhibits fewer specific granules and a lower mature score. Gene ontology (GO) analysis reveals that genes involved in cytokine-mediated signaling are downregulated in the Neu-5 cluster. Furthermore, we identify the Ccrl2 gene is specifically upregulated in this subgroup, which is confirmed by flow cytometry in AD mice. Finally, immunohistochemical staining indicates that CCRL2 protein is increased in the brains of AD mice.
CONCLUSIONS
We identify a unique CCRL2 positive neutrophil cluster, that is specifically enriched in the peripheral blood of AD mice.
PubMed: 38918830
DOI: 10.1186/s12979-024-00448-x -
Journal of Neurodevelopmental Disorders Jun 2024Minor physical anomalies (MPAs) are congenital morphological abnormalities linked to disruptions of fetal development. MPAs are common in 22q11.2 deletion syndrome...
BACKGROUND
Minor physical anomalies (MPAs) are congenital morphological abnormalities linked to disruptions of fetal development. MPAs are common in 22q11.2 deletion syndrome (22q11DS) and psychosis spectrum disorders (PS) and likely represent a disruption of early embryologic development that may help identify overlapping mechanisms linked to psychosis in these disorders.
METHODS
Here, 2D digital photographs were collected from 22q11DS (n = 150), PS (n = 55), and typically developing (TD; n = 93) individuals. Photographs were analyzed using two computer-vision techniques: (1) DeepGestalt algorithm (Face2Gene (F2G)) technology to identify the presence of genetically mediated facial disorders, and (2) Emotrics-a semi-automated machine learning technique that localizes and measures facial features.
RESULTS
F2G reliably identified patients with 22q11DS; faces of PS patients were matched to several genetic conditions including FragileX and 22q11DS. PCA-derived factor loadings of all F2G scores indicated unique and overlapping facial patterns that were related to both 22q11DS and PS. Regional facial measurements of the eyes and nose were smaller in 22q11DS as compared to TD, while PS showed intermediate measurements.
CONCLUSIONS
The extent to which craniofacial dysmorphology 22q11DS and PS overlapping and evident before the impairment or distress of sub-psychotic symptoms may allow us to identify at-risk youths more reliably and at an earlier stage of development.
Topics: Humans; DiGeorge Syndrome; Psychotic Disorders; Female; Male; Adolescent; Child; Craniofacial Abnormalities; Young Adult; Adult; Machine Learning; Image Processing, Computer-Assisted
PubMed: 38918700
DOI: 10.1186/s11689-024-09547-8 -
Comprehensive Psychiatry Jun 2024The COVID-19 pandemic has profoundly impacted the economic, psychological, and social well-being of people in Ethiopia. Pandemic-related fears can exacerbate anxiety and...
BACKGROUND
The COVID-19 pandemic has profoundly impacted the economic, psychological, and social well-being of people in Ethiopia. Pandemic-related fears can exacerbate anxiety and depression symptoms among those with pre-existing physical and mental health conditions as well as those with prior exposure to traumatic events.
METHODS
We used data from the Ethiopia NeuroGAP-Psychosis study (898 cases and 941 controls with and without a diagnosis of psychosis respectively, 66% male, mean age = 37 years). Data was collected between November 2021 and June 2022 during the COVID-19 pandemic from four hospitals in Ethiopia (three in Addis Ababa and one in Jimma city). Structural equation modeling analysis was conducted to examine the associations between trauma exposure, physical health conditions (like arthristis, neurological disorders, diabetes), COVID-19 stress, and psychological distress (depression and anxiety symptoms). We assessed direct and indirect effects for mediation, and conducted multigroup analysis to examine moderation by case control status.
RESULTS
We found evidence that the impact of greater trauma exposure and physical health conditions on higher psychological distress was mediated through higher COVID-19 stress. Sociodemographic characteristics (older age and being maried) were associated with higher psychological distress, with these associations mediated through greater trauma, physical health conditions, and COVID-19 stress. Case-control status also moderated the associations between these variables, with the mediation effects being stronger in cases and weaker in controls. Further, cases reported greater trauma and psychological distress, while controls reported more physical health conditions and COVID-19 stress.
IMPLICATIONS
Our findings uniquely assess the interaction of health and emergency related factors in understudied settings like Ethiopia. They underscore the importance of including daily hardships and environmental stressors, along with prior trauma exposure, as risk factors for the assessment of mental health symptoms. This study has key implications for mental health screening and intervention research in response to complex emergency contexts like Ethiopia with a history of armed conflict in addition to the COVID-19 pandemic. Our findings can aid the development of targeted services that address the mental health of at-risk groups with pre-existing mental and physical health conditions.
PubMed: 38917710
DOI: 10.1016/j.comppsych.2024.152508 -
Systematic Reviews Jun 2024Non-invasive brain stimulation (NIBS) is a promising intervention for treatment-resistant schizophrenia. However, there are multiple available techniques and a...
BACKGROUND
Non-invasive brain stimulation (NIBS) is a promising intervention for treatment-resistant schizophrenia. However, there are multiple available techniques and a comprehensive synthesis of evidence is lacking. Thus, we will conduct a systematic review and network meta-analysis to investigate the comparative efficacy and safety of NIBS techniques as an add-on to antipsychotics for treatment-resistant schizophrenia.
METHODS
We will include single- and double-blind randomized-controlled trials (RCT) comparing any NIBS technique with each other or with a control intervention as an add-on to antipsychotics in adult patients with treatment-resistant schizophrenia. We will exclude studies focusing on predominant negative symptoms, maintenance treatment, and single sessions. The primary outcome will be a change in overall symptoms, and secondary outcomes will be a change in symptom domains, cognitive performance, quality of life, functioning, response, dropouts, and side effects. We will search for eligible studies in previous reviews, multiple electronic databases and clinical trial registries from inception onwards. At least two independent reviewers will perform the study selection, data extraction, and risk of bias assessment. We will measure the treatment differences using standardized mean difference (SMD) and odds ratio (OR) for continuous and dichotomous outcomes, respectively. We will conduct pairwise and network meta-analysis within a frequentist framework using a random-effects model, except for rare event outcomes where we will use a fixed-effects Mantel-Haenszel method. We will investigate potential sources of heterogeneity in subgroup analyses. Reporting bias will be assessed with funnel plots and the Risk of Bias due to Missing Evidence in Network meta-analysis (ROB-MEN) tool. The certainty in the evidence will be evaluated using the Confidence in Network Meta-analysis (CINeMA) approach.
DISCUSSION
Our network meta-analysis would provide an up-to-date synthesis of the evidence from all available RCTs on the comparative efficacy and safety of NIBS for treatment-resistant schizophrenia. This information could guide evidence-based clinical practice and improve the outcomes of patients.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO-ID CRD42023410645.
Topics: Humans; Systematic Reviews as Topic; Network Meta-Analysis; Schizophrenia, Treatment-Resistant; Transcranial Direct Current Stimulation; Antipsychotic Agents; Transcranial Magnetic Stimulation; Meta-Analysis as Topic; Randomized Controlled Trials as Topic; Schizophrenia
PubMed: 38915121
DOI: 10.1186/s13643-024-02585-2 -
The Clinical Neuropsychologist Jun 2024Multiple sclerosis (MS) may include not only severe neurological signs and symptoms, but also cognitive and psychiatric disturbances. When psychiatric symptoms precede...
Multiple sclerosis (MS) may include not only severe neurological signs and symptoms, but also cognitive and psychiatric disturbances. When psychiatric symptoms precede or are comorbid with MS, it poses a clinical challenge, because it may lead to a mistaken diagnosis of MS as a psychiatric disorder, delaying proper treatment. We describe the neuropsychological profile of a female patient with MS whose diagnosis was delayed due to neuropsychiatric symptoms. : A comprehensive analysis of the medical history and the results of a teleneuropsychological assessment of a 36-year-old Mexican woman with a diagnosis of relapsing--remitting MS (RRMS) was performed. : The patient indicates a long history of psychotic, anxious, and depressive features years before the first neurological symptom that led to MS going unnoticed for several years. Language, attentional, perceptual, motor, and learning skills were found to be preserved. Short-term memory and spatial orientation problems were identified, with decreased processing speed and executive dysfunction, including working memory and planning deficits. : The patient has a non-typical presentation of neuropsychological alterations with cognitive and behavioral symptoms that resemble dorsolateral frontal lobe syndrome. This case study highlights the importance of considering MS in differential diagnosis of patients with psychiatric symptoms, even in the absence of obvious neurological signs.
PubMed: 38914594
DOI: 10.1080/13854046.2024.2370963