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IBRO Neuroscience Reports Jun 2024Neural network-level changes underlying symptom remission in major depressive disorder (MDD) are often studied from a single perspective. Multimodal approaches to assess...
Neural network-level changes underlying symptom remission in major depressive disorder (MDD) are often studied from a single perspective. Multimodal approaches to assess neuropsychiatric disorders are evolving, as they offer richer information about brain networks. A pipeline was developed to integrate a computationally intense data fusion method with a toolbox, to produce a faster and more intuitive pipeline for combining functional connectivity with structural connectivity (denoted as anatomically weighted functional connectivity ()). Ninety-three participants from the Canadian Biomarker Integration Network for Depression study (CAN-BIND-1) were included. Patients with MDD were treated with 8 weeks of escitalopram and adjunctive aripiprazole for another 8 weeks. Between-group connectivity (SC, FC, ) comparisons contrasted remitters (REM) with non-remitters (NREM) at baseline and 8 weeks. Additionally, a longitudinal study analysis was performed to compare connectivity changes across time for REM, from baseline to week-8. Association between cognitive variables and connectivity were also assessed. REM were distinguished from NREM by lower within the default mode, frontoparietal, and ventral attention networks. Compared to REM at baseline, REM at week-8 revealed increased within the dorsal attention network and decreased awFC within the frontoparietal network. A medium effect size was observed for most results. in the frontoparietal network was associated with neurocognitive index and cognitive flexibility for the NREM group at week-8. In conclusion, the pipeline has the benefit of providing insight on the 'full picture' of connectivity changes for REMs and NREMs while making for an easy intuitive approach.
PubMed: 38293679
DOI: 10.1016/j.ibneur.2023.12.011 -
Frontiers in Psychiatry 2024Periventricular heterotopia (PH) is a developmental malformation in the brain. Because the clinical symptoms are heterogeneous, few studies have investigated the...
Periventricular heterotopia (PH) is a developmental malformation in the brain. Because the clinical symptoms are heterogeneous, few studies have investigated the psychiatric symptoms associated with PH. We describe the case of a 17-year-old male with bipolar disorder (BD), who had been treated for attention deficit-hyperactivity disorder (ADHD) and developmental delay in childhood. He had experienced depression for 1 year and was admitted to the emergency room following a suicide attempt. He was admitted to the psychiatric ward for further evaluation and treatment for elated mood, decreased need for sleep, increased sexuality, and delusion. The patient was diagnosed with BP-I disorder and PH via brain magnetic resonance imaging. After combined treatment with valproic acid and aripiprazole, his manic symptoms stabilized. To our knowledge, this is the first report of an adolescent PH case with a history of early onset BD and ADHD in childhood.
PubMed: 38283846
DOI: 10.3389/fpsyt.2024.1289850 -
Cureus Dec 2023Methadone withdrawal usually presents as a classical opiate withdrawal syndrome, including symptoms such as restlessness, pupillary dilation, sweating, insomnia,...
Methadone withdrawal usually presents as a classical opiate withdrawal syndrome, including symptoms such as restlessness, pupillary dilation, sweating, insomnia, irritability, sneezing, nausea, vomiting, and diarrhea. It rarely manifests as psychosis. Here, we discuss the case of a 43-year-old female with a history of long-term methadone use who presented with first-episode psychosis during methadone down-titration. She exhibited persecutory delusions and auditory hallucinations, unrelated to classical opiate withdrawal symptoms. Medical tests were unremarkable. The patient was diagnosed with first-episode psychosis and was involuntarily admitted to our psychiatric hospital. As she suffered from hormone-dependent breast cancer and presented paliperidone-induced hyperprolactinemia, we switched this drug to aripiprazole, a prolactin-sparing antipsychotic. Her psychotic symptoms remitted in six weeks, with no reintroduction of methadone. It remains unclear whether this presentation is attributable to a rare manifestation of withdrawal or methadone's antipsychotic properties, masking an underlying psychotic disorder. This case contributes to understanding psychosis emergence post-opioid withdrawal, underscoring the need for further investigation into withdrawal-related psychosis and opioid antipsychotic properties. It also prompts the discussion of antipsychotic treatment in patients with comorbid breast cancer, while evidence about hyperprolactinemia as a risk factor for breast cancer remains conflicting.
PubMed: 38283524
DOI: 10.7759/cureus.51240 -
Molecular Autism Jan 2024Numerous interventions for irritability in autism spectrum disorder (ASD) have been investigated. We aimed to appraise the magnitude of pharmacological and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Numerous interventions for irritability in autism spectrum disorder (ASD) have been investigated. We aimed to appraise the magnitude of pharmacological and non-pharmacological interventions for irritability in ASD without any restrictions in terms of eligible interventions.
METHODS
We systematically searched PubMed/MEDLINE, Scopus, and Web of Science until April 15, 2023. We included randomized controlled trials (RCTs) with a parallel design that examined the efficacy of interventions for the treatment of irritability in patients of any age with ASD without any restrictions in terms of eligible interventions. We performed a random-effects meta-analysis by pooling effect sizes as Hedges' g. We classified assessed interventions as follows: pharmacological monotherapy, risperidone plus adjuvant therapy versus risperidone monotherapy, non-pharmacological intervention, and dietary intervention. We utilized the Cochrane tool to evaluate the risk of bias in each study and the GRADE approach to assess the certainty of evidence for each meta-analyzed intervention.
RESULTS
Out of 5640 references, we identified 60 eligible articles with 45 different kinds of interventions, including 3531 participants, of which 80.9% were males (mean age [SD] = 8.79 [3.85]). For pharmacological monotherapy, risperidone (Hedges' g - 0.857, 95% CI - 1.263 to - 0.451, certainty of evidence: high) and aripiprazole (Hedges' g - 0.559, 95% CI - 0.767 to - 0.351, certainty of evidence: high) outperformed placebo. Among the non-pharmacological interventions, parent training (Hedges' g - 0.893, 95% CI - 1.184 to - 0.602, certainty of evidence: moderate) showed a significant result. None of the meta-analyzed interventions yielded significant effects among risperidone + adjuvant therapy and dietary supplementation. However, several novel molecules in augmentation to risperidone outperformed risperidone monotherapy, yet from one RCT each.
LIMITATIONS
First, various tools have been utilized to measure the irritability in ASD, which may contribute to the heterogeneity of the outcomes. Second, meta-analyses for each intervention included only a small number of studies and participants.
CONCLUSIONS
Only risperidone, aripiprazole among pharmacological interventions, and parent training among non-pharmacological interventions can be recommended for irritability in ASD. As an augmentation to risperidone, several novel treatments show promising effects, but further RCTs are needed to replicate findings. Trial registration PROSPERO, CRD42021243965.
Topics: Male; Humans; Female; GRADE Approach; Aripiprazole; Risperidone; Autism Spectrum Disorder
PubMed: 38263251
DOI: 10.1186/s13229-024-00585-6 -
Frontiers in Psychiatry 2023Burning mouth syndrome (BMS) is characterized by persistent oral burning sensations without corresponding organic findings. Dementia with Lewy bodies (DLB) is a common...
Burning mouth syndrome (BMS) is characterized by persistent oral burning sensations without corresponding organic findings. Dementia with Lewy bodies (DLB) is a common type of dementia and generally presents visual hallucination and parkinsonism as motor dysfunction besides cognitive decline. In this case report, we present a case in which DLB emerged during the treatment for BMS, with a relatively positive outcome for BMS. A 74 years-old female complained of burning pain in her mouth and a subsequent decrease in food intake. Following a diagnosis of BMS, pharmacotherapy was initiated. BMS was much improved with mirtazapine 15 mg and aripiprazole 1.0 mg, leading to the restoration of her food intake by day 180. However, BMS flared up again triggered by deteriorating physical condition of herself and that of her husband. With aripiprazole 1.5 mg and amitriptyline 25 mg, her BMS gradually improved by day 482. However, by day 510, an increase in anxiety was noted, accompanied by the occasionally misidentification of her husband on day 566. Her cognitive impairment and disorientation were also reported by her husband on the day 572, she was then immediately referred to a neurologist specialized dementia and diagnosed with DLB on the day 583. Her treatment was adjusted to include the prescription of rivastigmine which was titrated up to 9.0 mg. Considering the potential impact of amitriptyline on cognitive function, it was reduced and switched to mirtazapine; however, her oral sensations slightly got worse. Following the consultation with her neurologist, amitriptyline 10 mg was reintroduced and aripiprazole was discontinued on day 755. Remarkably, BMS gradually improved without deteriorating DLB. This case indicated the reaffirmed necessity of careful interviews for changes in daily life not only with the patients but also with their families through the medical assessments. It highlights the vigilance regarding potential cognitive decline underlying or induced as an adverse event especially when treating elderly patients with BMS. While the interaction between BMS and DLB remains unclear, this case underscores the importance of prudent diagnosis and constructing collaboration with specialists in managing BMS with the early phase of DLB.
PubMed: 38260804
DOI: 10.3389/fpsyt.2023.1329171 -
Cureus Dec 2023Delusional companion syndrome, an uncommon subtype of delusional misidentification syndrome, has no prior reported cases in patients with primary psychotic disorders. We...
Delusional companion syndrome, an uncommon subtype of delusional misidentification syndrome, has no prior reported cases in patients with primary psychotic disorders. We report a case of delusional companion syndrome in the absence of any organic brain disease, stroke, or severe brain injury, in a young female with schizophrenia. The patient is a 29-year-old G3P3 female, with a history of schizophrenia and major depressive disorder, who, after recently losing custody of her children, presented to the pediatric emergency department for evaluation of her baby doll, which she believed to be her child because the doll wasn't eating or moving well. She became acutely agitated when providers declined to insert an IV line to hydrate the doll and required emergency treatment orders to de-escalate. The patient was admitted to the inpatient psychiatric unit and treated with oral aripiprazole 10 mg, before transitioning to her previous treatment of aripiprazole lauroxil at an increased dose of 882 mg monthly. By the end of admission, the patient grasped that the doll was a toy that had never been alive. This case demonstrates how delusional companion syndrome can occur in young patients with primary psychotic disorders, without a causative neurological insult, and can be treated with antipsychotics. More studies are necessary to further explore the relationship between primary psychotic disorders and delusional companion syndrome.
PubMed: 38259370
DOI: 10.7759/cureus.51007 -
Pharmaceutics Jan 2024Therapeutic drug monitoring improves the benefit-risk balance of antipsychotic therapy. Ultra-high-performance liquid chromatography-tandem mass spectrometry...
Therapeutic drug monitoring improves the benefit-risk balance of antipsychotic therapy. Ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) is considered the gold-standard method for measuring plasma drug concentrations; however, the Alinity C system has emerged as a promising alternative. This is the first study aimed at comparing UHPLC-MS/MS versus Alinity C in measuring plasma concentrations of aripiprazole and dehydroaripiprazole. A total of 86 plasma samples were analyzed. The active moiety of aripiprazole was measured in 60 samples using both systems and 26 samples were analyzed twice using Alinity C with an intermediate period of 6 months to assess its reproducibility. Spearman's correlation revealed a good association between the two assays (rs = 0.96) and no significance differences were found by McNemar's test when classifying samples between infra-, supra- and therapeutic ranges. Passing-Bablock regression showed a good correlation among methods (rs = 0.93) and a slope of 1.12 indicating a slight tendency of Alinity C to measure higher values than UHPLC-MS/MS. In addition, a good intra-method correlation across the two sequential analyses with Alinity C was obtained (rs = 0.99). Nonetheless, clinical decisions could be different in 15% of the cases depending on the chosen method. No differences were found in active moiety determination by Alinity C depending on the concentration of aripiprazole and dehydroaripiprazole of the samples.
PubMed: 38258114
DOI: 10.3390/pharmaceutics16010104 -
Medicina (Kaunas, Lithuania) Dec 2023: Aripiprazole (APZ), an atypical antipsychotic, is mainly prescribed for conditions such as schizophrenia and bipolar disorder, while ongoing research indicates...
: Aripiprazole (APZ), an atypical antipsychotic, is mainly prescribed for conditions such as schizophrenia and bipolar disorder, while ongoing research indicates promising neuroprotective qualities. APZ's mechanism of action, involving the regulation of neurotransmitter levels, appears to contribute to its potential to shield neural tissues from specific forms of harm and degeneration. : To investigate its neuroprotective mechanisms, groups of rats were orally administered APZ at 1 or 2 mg/kg once daily for a 30-day period. In addition, neuronal toxicity was induced through intraperitoneal injection of four doses of lipopolysaccharide (LPS) at a concentration of 1 mg/kg. To evaluate cognitive function, particularly, short-term recognition memory, the procedure implemented the novel object recognition (NOR) task. Subsequently, brain tissues were gathered to examine markers linked with neuroinflammation, oxidative stress, and apoptosis. : The administration of LPS led to a decline in memory performance during the NOR tasks. Simultaneously, this LPS treatment raised inflammatory markers like cyclooxygenase (COX)-2, tumor necrosis factor (TNF)-α, and nuclear factor kappa B (NF-κB), increased oxidative markers such as malondialdehyde (MDA), and triggered apoptosis markers like Caspase-3 and Bcl2 associated X protein (Bax) within the brain. Furthermore, it decreased levels of antioxidants like reduced glutathione (GSH) and catalase, as well as the anti-apoptotic marker B-cell lymphoma (Bcl)-2 in brain tissue. The use of APZ resulted in enhanced recognition memory performance, as indicated by improved exploration and discrimination abilities of the objects in the NOR task. Moreover, APZ lowered the markers associated with neuronal vulnerability, such as COX-2, NF-κB, MDA, Caspase-3, and Bax. Additionally, it increased the levels of protective markers, including GSH, catalase, and Bcl-2 in LPS-challenged brains. : In summary, the findings suggest that APZ exhibits protective properties against neuronal inflammation, oxidative stress, and apoptosis markers in the context of inflammatory-related neurodegeneration. Additional in-depth investigations are needed to further explore potential applications.
Topics: Animals; Rats; Aripiprazole; Lipopolysaccharides; bcl-2-Associated X Protein; Caspase 3; Catalase; NF-kappa B; Cognitive Dysfunction; Oxidative Stress; Inflammation; Apoptosis; Cyclooxygenase 2
PubMed: 38256307
DOI: 10.3390/medicina60010046 -
International Journal of Molecular... Jan 2024The available antipsychotics for schizophrenia (SZ) only reduce positive symptoms and do not significantly modify SZ neurobiology. This has raised the question of the...
Differential Effects of Aripiprazole on Electroencephalography-Recorded Gamma-Band Auditory Steady-State Response, Spontaneous Gamma Oscillations and Behavior in a Schizophrenia Rat Model.
The available antipsychotics for schizophrenia (SZ) only reduce positive symptoms and do not significantly modify SZ neurobiology. This has raised the question of the robustness and translational value of methods employed during drug development. Electroencephalography (EEG)-based measures like evoked and spontaneous gamma oscillations are considered robust translational biomarkers as they can be recorded in both patients and animal models to probe a key mechanism underlying all SZ symptoms: the excitation/inhibition imbalance mediated by N-methyl-D-aspartate receptor (NMDAr) hypofunction. Understanding the effects of commercialized atypical antipsychotics on such measures could therefore contribute to developing better therapies for SZ. Yet, the effects of such drugs on these EEG readouts are unknown. Here, we studied the effect of the atypical antipsychotic aripiprazole on the gamma-band auditory steady-state response (ASSR), spontaneous gamma oscillations and behavioral features in a SZ rat model induced by the NMDAr antagonist MK-801. Interestingly, we found that aripiprazole could not normalize MK-801-induced abnormalities in ASSR, spontaneous gamma oscillations or social interaction while it still improved MK-801-induced hyperactivity. Suggesting that aripiprazole is unable to normalize electrophysiological features underlying SZ symptoms, our results might explain aripiprazole's inefficacy towards the social interaction deficit in our model but also its limited efficacy against social symptoms in patients.
Topics: Humans; Animals; Rats; Aripiprazole; Schizophrenia; Dizocilpine Maleate; Antipsychotic Agents; Electroencephalography; Receptors, N-Methyl-D-Aspartate
PubMed: 38256109
DOI: 10.3390/ijms25021035 -
Biomedicines Jan 2024This research studies the dose-plasma level (PL) relationship of second-generation antipsychotics, together with the treatment outcomes achieved, in seriously ill people...
This research studies the dose-plasma level (PL) relationship of second-generation antipsychotics, together with the treatment outcomes achieved, in seriously ill people with schizophrenia. An observational, prospective, one-year follow-up study was carried out with patients (N = 68) with severe schizophrenia treated with paliperidone three-month (PP3M) or aripiprazole one-month (ARIM). Participants were divided into standard-dose or high-dose groups. PLs were divided into "standard PL" and "high PL" (above the therapeutic reference range, TRR) groups. The dose/PL relationship, and severity, hospitalizations, tolerability, compliance, and their relationship with doses and PLs were evaluated. There was no clear linear relationship between ARIM or PP3M doses and the PLs achieved. In half of the subjects, standard doses reached PLs above the TRR. The improvements in clinical outcomes (decrease in clinical severity and relapses) were related to high PLs, without worse treatment tolerability or adherence. All participants remained in the study, regardless of dose or PL. Clinical severity and hospitalizations decreased significantly more in those patients with high PLs. Considering the non-linear dose-PL relationship of ARIM and PP3M in people with severe schizophrenia, PLs above the TRR are linked to better treatment outcomes, without worse tolerability. The need in a notable number of cases for high doses to reach those effective PLs is highlighted.
PubMed: 38255270
DOI: 10.3390/biomedicines12010165