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NeuroImage Jun 2024Numerous studies show that electroconvulsive therapy (ECT) induces hippocampal neuroplasticity, but findings are inconsistent regarding its clinical relevance. This...
BACKGROUND
Numerous studies show that electroconvulsive therapy (ECT) induces hippocampal neuroplasticity, but findings are inconsistent regarding its clinical relevance. This study aims to investigate ECT-induced plasticity of anterior and posterior hippocampi using mathematical complexity measures in neuroimaging, namely Higuchi's fractal dimension (HFD) for fMRI time series and the fractal dimension of cortical morphology (FD-CM). Furthermore, we explore the potential of these complexity measures to predict ECT treatment response.
METHODS
Twenty patients with a current depressive episode (16 with major depressive disorder and 4 with bipolar disorder) underwent MRI-scans before and after an ECT-series. Twenty healthy controls matched for age and sex were also scanned twice for comparison purposes. Resting-state fMRI data were processed, and HFD was computed for anterior and posterior hippocampi. Group-by-time effects for HFD in anterior and posterior hippocampi were calculated and correlations between HFD changes and improvement in depression severity were examined. For FD-CM analyses, we preprocessed structural MRI with CAT12's surface-based methods. We explored group-by-time effects for FD-CM and the predictive value of baseline HFD and FD-CM for treatment outcome.
RESULTS
Patients exhibited a significant increase in bilateral hippocampal HFD from baseline to follow-up scans. Right anterior hippocampal HFD increase was associated with reductions in depression severity. We found no group differences and group-by-time effects in FD-CM. After applying a whole-brain regression analysis, we found that baseline FD-CM in the left temporal pole predicted reduction of overall depression severity after ECT. Baseline hippocampal HFD did not predict treatment outcome.
CONCLUSION
This study suggests that HFD and FD-CM are promising imaging markers to investigate ECT-induced neuroplasticity associated with treatment response.
PubMed: 38901774
DOI: 10.1016/j.neuroimage.2024.120671 -
Cureus May 2024The aim of this study is to investigate sexual dysfunctions (SDs) and related factors in patients with schizophrenia and bipolar disorder receiving pharmacotherapy.
OBJECTIVE
The aim of this study is to investigate sexual dysfunctions (SDs) and related factors in patients with schizophrenia and bipolar disorder receiving pharmacotherapy.
METHODS
This study included 111 patients. The Scale for the Assessment of Positive Symptoms (SAPS), the Scale for the Assessment of Negative Symptoms (SANS), and the Calgary Depression Scale for Schizophrenia (CDSS) were applied to the schizophrenia, and the Young Mania Rating Scale (YMRS) and Hamilton Depression Rating Scale (HAM-D) to the bipolar patient group. The sociodemographic data form and the Arizona Sexual Experiences Scale (ASEX) were applied to both of the patient groups. Blood was drawn from all patients to evaluate the indicated gene polymorphisms and evaluate prolactin levels.
RESULTS
SD was detected in 45.9% (N = 34) of the schizophrenia group, and 59.5% (N = 22) in the bipolar disorder group. SD was significantly higher in elderly patients and patients with a high smoking amount and low education levels. The eNOS -786T>C T allele frequency was found to be significantly higher in patients with SD. The logistic regression analysis determined that eNOS -786T>C CT and TT genotypes increased the risk of SD.
CONCLUSION
In this study, the high rates of SD in patients with schizophrenia and bipolar disorder, and the presence of modifiable factors that influence the presence of SD, suggest that SD should be given more attention in these patient groups. On the other hand, the high rate of SD in patients with the eNOS -786T>C T allele indicates the importance of carrying out new studies investigating the factors affecting the enzyme activity in this genotype. There is a need for more studies on eNOS genotypes and enzyme activites in this area.
PubMed: 38899233
DOI: 10.7759/cureus.60654 -
Journal of Affective Disorders Jun 2024Repetitive transcranial magnetic stimulation (rTMS) is a rapidly emerging treatment for depression, but outcome prediction is still a challenge. This study aimed to...
BACKGROUND
Repetitive transcranial magnetic stimulation (rTMS) is a rapidly emerging treatment for depression, but outcome prediction is still a challenge. This study aimed to identify predictors of response to rTMS among baseline clinical factors and early symptomatic improvements.
METHODS
This cohort study comprised 136 patients with a unipolar or bipolar depressive episode referred for clinical intermittent theta-burst stimulation or right-sided 1 Hz rTMS at the Uppsala Brain Stimulation Unit. The co-primary outcomes used for logistic regression were response, defined as ≥50 % reduction of Montgomery and Åsberg Depression Rating Scale Self-assessment (MADRS-S) total score, and 1-2 points on the Clinical Global Impression Improvement (CGI-I) scale. Early improvement was defined as ≥20 % reduction in the MADRS-S total score, or ≥ 1 point reduction in each MADRS-S item, after two weeks of treatment.
RESULTS
The response rates were 21 % for MADRS-S and 45 % for CGI-I. A depressive episode >24 months had lower odds for MADRS-S response compared to ≤12 months. Early improvement of the MADRS-S total score predicted CGI-I response (95 % CI = 1.35-9.47, p = 0.011), Initiative predicted MADRS-S response (95 % CI = 1.08-9.05, p = 0.035), and Emotional involvement predicted CGI-I response (95 % CI = 1.03-8.66, p = 0.044).
LIMITATIONS
No adjustment for concurrent medication.
CONCLUSIONS
A depressive episode ≤12 months and early improvement in overall depressive symptoms, as well as the individual items, Initiative and Emotional involvement, predicted subsequent rTMS response in a naturalistic sample of depressed patients. This could facilitate the early identification of patients who will benefit from further rTMS sessions.
PubMed: 38897300
DOI: 10.1016/j.jad.2024.06.054 -
Psychiatry Research Jun 2024The impact of traumatic brain injury (TBI) on subsequent risk of schizophrenia (SCZ) or bipolar disorder (BD) remains contested. Possible genetic and environmental...
The impact of traumatic brain injury (TBI) on subsequent risk of schizophrenia (SCZ) or bipolar disorder (BD) remains contested. Possible genetic and environmental confounding effects have also been understudied. Therefore, we aim to investigate the impact of TBI on the risk of SCZ and BD and whether the effect varies by injury severity, age at injury, and sex. We identified 4,184 SCZ and 18,681 BD cases born between 1973 and 1998 in the Swedish National Registers. Case-control samples matched (1:5) on birth year, sex, and birthplace were created along with a family design study, with cases matched to non-case full siblings. TBI was associated with higher risk of SCZ and BD (IRR=1.33 for SCZ, IRR=1.78 for BD). The association remained significant in the sibling comparison study. Moderate or severe TBI was associated with higher risk for both SCZ and BD compared to mild TBI. Older age at injury was associated with higher risk of SCZ and BD, and the effect of TBI was stronger in women than men. Findings indicate that TBI is a risk factor for both SCZ and BD with differential impact by age, severity and sex and that this association cannot be explained by familial confounding alone.
PubMed: 38896929
DOI: 10.1016/j.psychres.2024.115990 -
Frontiers in Psychiatry 2024Psychotic symptoms are among the most debilitating and challenging presentations of severe psychiatric diseases, such as schizophrenia, schizoaffective, and bipolar...
UNLABELLED
Psychotic symptoms are among the most debilitating and challenging presentations of severe psychiatric diseases, such as schizophrenia, schizoaffective, and bipolar disorder. A pathophysiological understanding of intrinsic brain activity underlying psychosis is crucial to improve diagnosis and treatment. While a potential continuum along the psychotic spectrum has been recently described in neuroimaging studies, especially for what concerns absolute and relative amplitude of low-frequency fluctuations (ALFF and fALFF), these efforts have given heterogeneous results. A transdiagnostic meta-analysis of ALFF/fALFF in patients with psychosis compared to healthy controls is currently lacking. Therefore, in this pre-registered systematic review and meta-analysis PubMed, Scopus, and Embase were searched for articles comparing ALFF/fALFF between psychotic patients and healthy controls. A quantitative synthesis of differences in (f)ALFF between patients along the psychotic spectrum and healthy controls was performed with Seed-based d Mapping, adjusting for age, sex, duration of illness, clinical severity. All results were corrected for multiple comparisons by Family-Wise Error rates. While lower ALFF and fALFF were detected in patients with psychosis in comparison to controls, no specific finding survived correction for multiple comparisons. Lack of this correction might explain the discordant findings highlighted in previous literature. Other potential explanations include methodological issues, such as the lack of standardization in pre-processing or analytical procedures among studies. Future research on ALFF/fALFF differences for patients with psychosis should prioritize the replicability of individual studies.
SYSTEMATIC REVIEW REGISTRATION
https://osf.io/, identifier (ycqpz).
PubMed: 38895037
DOI: 10.3389/fpsyt.2024.1378439 -
Frontiers in Psychiatry 2024Depressive episodes with psychotic symptoms are prevalent among the older adults, emphasizing the need to differentiate them from dementia with Lewy bodies (DLB), in...
Depressive episodes with psychotic symptoms are prevalent among the older adults, emphasizing the need to differentiate them from dementia with Lewy bodies (DLB), in which depressive and psychotic symptoms commonly coexist. In contrast, psychotic symptoms occur more frequently in depressive episodes of bipolar disorder (BD) than in major depressive disorder (MDD). Although MDD is a significant risk factor for dementia, studies exploring the relationship between BD and dementia are lacking. This report details the case of a 74-year-old female who experienced severe psychotic depression that led to suicide attempts during a long-term course of young-onset BD. Ultimately, she was diagnosed with DLB based on her neurocognitive symptoms and results of the neuroimaging examination. She had experienced multiple relapses in the past, predominantly characterized by depressive episodes in her old age. Notably, she had never undergone lithium treatment, which is known for its potential efficacy in preventing relapse and dementia. Recent systematic reviews and meta-analyses have suggested that patients with BD have a higher risk of dementia than the general population, and that lithium usage is associated with a reduced risk. Moreover, patients with BD have been suggested to have an elevated risk of developing Parkinson's disease (PD), and the pathophysiological relationship between BD and PD may be attributed to dopamine dysregulation resulting from multiple relapses. Future research is imperative to identify strategies for preventing dementia in patients with BD and to develop interventions for the comorbidities of BD and DLB.
PubMed: 38895028
DOI: 10.3389/fpsyt.2024.1409027 -
Diagnostics (Basel, Switzerland) May 2024Although magnetic resonance spectroscopy (MRS) has provided in vivo measurements of brain chemical profiles in bipolar disorder (BD), there are no data on clinically and...
Although magnetic resonance spectroscopy (MRS) has provided in vivo measurements of brain chemical profiles in bipolar disorder (BD), there are no data on clinically and therapeutically important onset polarity (OP) and predominant polarity (PP). We conducted a proton MRS study in BD polarity subphenotypes, focusing on emotion regulation brain regions. Forty-one euthymic BD patients stratified according to OP and PP and sixteen healthy controls (HC) were compared. 1H-MRS spectra of the anterior and posterior cingulate cortex (ACC, PCC), left and right hippocampus (LHIPPO, RHIPPO) were acquired at 3.0T to determine metabolite concentrations. We found significant main effects of OP in ACC mI, mI/tNAA, mI/tCr, mI/tCho, PCC tCho, and RHIPPO tNAA/tCho and tCho/tCr. Although PP had no significant main effects, several medium and large effect sizes emerged. Compared to HC, manic subphenotypes (i.e., manic-OP, manic-PP) showed greater differences in RHIPPO and PCC, whereas depressive suphenotypes (i.e., depressive-OP, depressive-PP) in ACC. Effect sizes were consistent between OP and PP as high intraclass correlation coefficients (ICC) were confirmed. Our findings support the utility of MRS in the study of the neurobiological underpinnings of OP and PP, highlighting that the regional specificity of metabolite changes within the emotion regulation network consistently marks both polarity subphenotypes.
PubMed: 38893696
DOI: 10.3390/diagnostics14111170 -
Nutrients May 2024The ketogenic diet (KD) has been highly developed in the past for the treatment of epileptic pathological states in children and adults. Recently, the current... (Review)
Review
The Potential Effects of the Ketogenic Diet in the Prevention and Co-Treatment of Stress, Anxiety, Depression, Schizophrenia, and Bipolar Disorder: From the Basic Research to the Clinical Practice.
BACKGROUND
The ketogenic diet (KD) has been highly developed in the past for the treatment of epileptic pathological states in children and adults. Recently, the current re-emergence in its popularity mainly focuses on the therapy of cardiometabolic diseases. The KD can also have anti-inflammatory and neuroprotective activities which may be applied to the prevention and/or co-treatment of a diverse range of psychiatric disorders.
PURPOSE
This is a comprehensive literature review that intends to critically collect and scrutinize the pre-existing research basis and clinical data of the potential advantageous impacts of a KD on stress, anxiety, depression, schizophrenia and bipolar disorder.
METHODS
This literature review was performed to thoroughly represent the existing research in this topic, as well as to find gaps in the international scientific community. In this aspect, we carefully investigated the ultimate scientific web databases, e.g., PubMed, Scopus, and Web of Science, to derive the currently available animal and clinical human surveys by using efficient and representative keywords.
RESULTS
Just in recent years, an increasing amount of animal and clinical human surveys have focused on investigating the possible impacts of the KD in the prevention and co-treatment of depression, anxiety, stress, schizophrenia, and bipolar disorder. Pre-existing basic research with animal studies has consistently demonstrated promising results of the KD, showing a propensity to ameliorate symptoms of depression, anxiety, stress, schizophrenia, and bipolar disorder. However, the translation of these findings to clinical settings presents a more complex issue. The majority of the currently available clinical surveys seem to be moderate, usually not controlled, and have mainly assessed the short-term effects of a KD. In addition, some clinical surveys appear to be characterized by enormous dropout rates and significant absence of compliance measurement, as well as an elevated amount of heterogeneity in their methodological design.
CONCLUSIONS
Although the currently available evidence seems promising, it is highly recommended to accomplish larger, long-term, randomized, double-blind, controlled clinical trials with a prospective design, in order to derive conclusive results as to whether KD could act as a potential preventative factor or even a co-treatment agent against stress, anxiety, depression, schizophrenia, and bipolar disorder. Basic research with animal studies is also recommended to examine the molecular mechanisms of KD against the above psychiatric diseases.
Topics: Humans; Diet, Ketogenic; Schizophrenia; Bipolar Disorder; Animals; Anxiety; Stress, Psychological; Depression
PubMed: 38892480
DOI: 10.3390/nu16111546 -
International Journal of Molecular... May 2024Suicide is a major public health priority, and its molecular mechanisms appear to be related to glial abnormalities and specific transcriptional changes. This study... (Review)
Review
Suicide is a major public health priority, and its molecular mechanisms appear to be related to glial abnormalities and specific transcriptional changes. This study aimed to identify and synthesize evidence of the relationship between glial dysfunction and suicidal behavior to understand the neurobiology of suicide. As of 26 January 2024, 46 articles that met the inclusion criteria were identified by searching PubMed and ISI Web of Science. Most postmortem studies, including 30 brain regions, have determined no density or number of total Nissl-glial cell changes in suicidal patients with major psychiatric disorders. There were 17 astrocytic, 14 microglial, and 9 oligodendroglial studies using specific markers of each glial cell and further on their specific gene expression. Those studies suggest that astrocytic and oligodendroglial cells lost but activated microglia in suicides with affective disorder, bipolar disorders, major depression disorders, or schizophrenia in comparison with non-suicided patients and non-psychiatric controls. Although the data from previous studies remain complex and cannot fully explain the effects of glial cell dysfunction related to suicidal behaviors, they provide risk directions potentially leading to suicide prevention.
Topics: Humans; Neuroglia; Suicide; Brain; Biomarkers; Autopsy; Suicidal Ideation; Bipolar Disorder
PubMed: 38891940
DOI: 10.3390/ijms25115750 -
International Journal of Molecular... May 2024Until the late 1800s, drug development was a chance finding based on observations and repeated trials and errors. Today, drug development must go through many iterations... (Review)
Review
Until the late 1800s, drug development was a chance finding based on observations and repeated trials and errors. Today, drug development must go through many iterations and tests to ensure it is safe, potent, and effective. This process is a long and costly endeavor, with many pitfalls and hurdles. The aim of the present review article is to explore what is needed for a molecule to move from the researcher bench to the patients' bedside, presented from an industry perspective through the development program of cariprazine. Cariprazine is a relatively novel antipsychotic medication, approved for the treatment of schizophrenia, bipolar mania, bipolar depression, and major depression as an add-on. It is a D3-preferring D3-D2 partial agonist with the highest binding to the D3 receptors compared to all other antipsychotics. Based on the example of cariprazine, there are several key factors that are needed for a molecule to move from the researcher bench to the patients' bedside, such as targeting an unmet medical need, having a novel mechanism of action, and a smart implementation of development plans.
Topics: Humans; Antipsychotic Agents; Piperazines; Receptors, Dopamine D3; Schizophrenia; Animals; Bipolar Disorder; Drug Development
PubMed: 38891871
DOI: 10.3390/ijms25115682