Major depressive disorder is one of the most common mental illnesses that highly impairs quality of life. Pharmacological interventions are mainly focused on altered monoamine neurotransmission, ...which is considered the primary event underlying the disease's etiology. However, many other neuropathological mechanisms that contribute to the disease's progression and clinical symptoms have been identified. These include oxidative stress, neuroinflammation, hippocampal atrophy, reduced synaptic plasticity and neurogenesis, the depletion of neurotrophic factors, and the dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis. Current therapeutic options are often unsatisfactory and associated with adverse effects. This review highlights the most relevant findings concerning the role of flavonols, a ubiquitous class of flavonoids in the human diet, as potential antidepressant agents. In general, flavonols are considered to be both an effective and safe therapeutic option in the management of depression, which is largely based on their prominent antioxidative and anti-inflammatory effects. Moreover, preclinical studies have provided evidence that they are capable of restoring the neuroendocrine control of the HPA axis, promoting neurogenesis, and alleviating depressive-like behavior. Although these findings are promising, they are still far from being implemented in clinical practice. Hence, further studies are needed to more comprehensively evaluate the potential of flavonols with respect to the improvement of clinical signs of depression.
Rationale
Beneficial effects of aripiprazole on cognition in schizophrenia have been previously reported, but not in recent onset schizophrenia. Cognitive impairments have also been associated with ...catechol-
O
-methyltransferase (COMT), methylenetetrahydrofolate reductase (MTHFR), and serotonin transporter (SERT) gene polymorphisms which were earlier implicated in the pathophysiology of schizophrenia.
Objectives
This study examined the short-term influence of aripiprazole long-acting injectable (LAI) as well as of COMT, MTHFR, and SERT gene polymorphisms and their interactions on clinical features and cognitive functions in inpatients with recent onset schizophrenia.
Methods
This study included 98 inpatients suffering from recent onset schizophrenia diagnosed according to DSM-5 criteria. Three months after initiating aripiprazole LAI, the severity of symptoms was assessed by the Positive and Negative Syndrome Scale (PANSS), while cognitive functions were measured by 5-KOG test for cognition. Genotypes of SERT, MTHFR, and COMT gene were determined by different polymerase chain reaction (PCR) methods.
Results
Three-month aripiprazole LAI treatment was associated with a statistically significant change of PANSS total (
p
<0.001) and subscale scores as well as cognitive parameters of delayed recall (
p
<0.03), attention (
p
<0.01), and executive functions in the form of less perseverations (
p
<0.03), without influencing other examined cognitive functions. However, it significantly influenced composite cognitive score (
p
<0.02). In regard to the investigated genetic polymorphisms, we established a positive association between the COMT polymorphism (M/M allele carriers) and attention (
p
<0.01). Additionally, we also established a positive association between the COMT – MTHFR interaction and attention (
p
<0.02), as well as perseveration item belonging to executive functions (
p
<0.01). Two other investigated polymorphisms (MTHFR and SERT) were not significantly associated with cognitive indices. Investigated genetic polymorphisms and their interactions were not associated with PANSS scores.
Conclusions
Our findings suggest that aripiprazole LAI improves individual cognitive functions in recent onset schizophrenia. Investigated COMT polymorphism (Met/Met genotype), as well as the COMT-MTHFR interaction, were positively associated with attention and executive functioning (perseveration), potentially implying COMT’s biomarker potential in terms of cognition in schizophrenia.
We investigated whether a functional insertion/deletion (I/D) polymorphism of angiotensin-converting enzyme (ACE) influenced antipsychotic treatment. At baseline, and after 8 weeks of treatment with ...various antipsychotic medications, we assessed patients’ Positive and Negative Syndrome Scale (PANSS) scores, PANSS factors, and metabolic-syndrome-related parameters (fasting plasma lipid and glucose levels, and body mass index). A total of 186 antipsychotic-naïve first-episode psychosis patients or nonadherent chronic psychosis individuals (99 males and 87 females) were genotyped by polymerase chain reaction analysis. The ACE-I/D polymorphism was significantly associated with changes in PANSS psychopathology only (p < 0.05). Compared to ACE-II homozygous males, ACE-DD homozygous and ACE-ID heterozygous males manifested significantly greater decreases in PANSS positive score, PANSS excitement factor, and PANSS cognitive factor. ACE-DD homozygous females manifested higher decreases in PANSS depression factor compared to ACE-II homozygous and ACE-ID heterozygous females. The polymorphism’s effect size was estimated as moderate to strong, while its contribution to the PANSS psychopathology ranged from ~5.4 to 8.7%, with the lowest contribution observed for PANSS positive score changes and the highest for PANSS depressive factor changes. Our results indicate that ACE-I/D polymorphism had a statistically significant but weak gender-specific impact on psychopathology data, and showed no association between ACE-I/D polymorphism and metabolic-syndrome-related parameters.
Objective Impaired serotonergic neurotransmission has been implicated in the pathogenesis of depression and schizophrenia. Blood platelets have been used for years as a peripheral model of neuronal ...serotonin dynamics. The objective was to investigate platelet count and serotonin concentration in patients with depression and schizophrenia, in an attempt to ascertain their clinical usefulness.Methods 953 participants were included in the study, 329 patients with depression, 339 patients with schizophrenia and 285 healthy controls. ELISA was used to assess platelet serotonin concentrations.Results There were no statistically significant differences among groups regarding age, total platelet count and serotonin concentration. Linear regression analyses revealed inverse correlations between platelet serotonin concentration and age of patients with depression and healthy individuals, as well as between platelet serotonin concentration and illness duration in patients with schizophrenia. In other words, longer illness duration in patients with schizophrenia, and higher age in patients with depression and healthy individuals was associated with lower platelet serotonin concentrations.Conclusion Platelet count and serotonin concentration did not prove to be of diagnostic value in differentiating patients and healthy individuals. However, illness duration in patients with schizophrenia may be associated with reduced concentrations of platelet serotonin.
Schizophrenia is a debilitating disease that disrupts the lives of many affected individuals and exerts a toll on the health system. Only few studies assessed once-monthly injectable formulation of ...paliperidone palmitate (PP-1M) and other long-acting antipsychotics in recent onset schizophrenia (ROS). To evaluate whether PP-1M is efficacious in reducing frequency and length of hospitalizations and psychosis symptom severity in patients with ROS.
This mirror-image study included 112 patients, suffering from ROS admitted in a psychiatric ward and successively treated with PP-1M for 1-year. Other psychotic disorders were excluded. We collected socio-demographic data of all subjects included, number and days of hospitalization, as well as Clinical Global Impression-Severity scale (CGI-S) and Clinician-Rated Dimensions of Psychosis Symptom Severity (CRDPSS) scores at the initiation and after 1-year of PP treatment.
After 1-year PP-1M treatment, mean scores of both CGI and CRDPSS significantly decreased (
< 0.001), as well as the mean number of hospitalizations (
= 0.002) and total hospitalization days (
< 0.001) in comparison with those of the previous year.
Our results suggest that PP-1M can be considered as an important therapeutic option in patients with ROS. Its use led to a meaningful reduction in the patient's use of hospital services, as well as a significant clinical improvement of psychotic symptoms in our sample.
Clozapine is considered the gold standard for patients with treatment-resistant schizophrenia (TRS) who have previously tried other antipsychotics at adequate doses (two or more, with at least one ...being atypical). However, despite optimal treatment, a subgroup of TRS patients with what is known as ultra-treatment-resistant schizophrenia (UTRS) fails to respond to clozapine, which occurs in 40-70% of cases. The most common approach to manage UTRS involves augmenting clozapine with pharmacological or non-pharmacological interventions, with a growing body of evidence that supports the use of electroconvulsive therapy (ECT) as an augmenter. This prospective non-randomized 8-week study, which followed the TRIPP Working Group guidelines and is one of few that separate TRS from UTRS, aimed to evaluate the effectiveness of clozapine in TRS patients and the efficacy of ECT augmentation of clozapine in UTRS patients. Patients with TRS were assigned to receive clozapine alone (clozapine group), whereas UTRS patients received bilateral ECT in addition to their current medication regimen (ECT plus clozapine group). The severity of symptoms was evaluated using the Clinical Global Impression Scale (CGI) and Positive and Negative Syndrome Scale (PANSS) at baseline and at the end of the 8-week trial. Both treatment approaches resulted in improved CGI and PANSS scores. The results suggest that both clozapine and ECT are effective treatment options for patients with TRS and UTRS, respectively, and that adherence to guidelines should provide a better frame for future clinical studies.
The use of electroretinography (ERG) and optical coherence tomography (OCT) has currently expanded beyond ophthalmology alone. The aim of this review is to present the results and knowledge acquired ...by these two methods in patients suffering from schizophrenia. Reviewing the studies applying ERG and OCT methods in the field of psychiatry, one can conclude that results of the research imply morphological and functional changes of retina in patients with schizophrenia that are not consistent. However, in most studies there was reduction of the amplitude and changes in the implicit time related parameters on ERG and thinning of the retinal nerve fiber layer on OCT. Neurons in the eye use the same neurotransmitters as neurons in the basal brain structures that are most affected in schizophrenia, according to the dopamine hypothesis of schizophrenia. Unlike neurons in the basal brain structures, the neurons in the eye are
in vivo
available to ERG. Using the aforementioned tests together with clinical diagnostic criteria of schizophrenia, the subgroups with different prognostic and therapeutic specificities within schizophrenia as a group of diseases might be identified more precisely.
Background: We investigated the potential use of SPECT quantification in addition to qualitative brain perfusion analysis for the detection of anti-NMDAR encephalitis. The question is how to ...normalize brain activity to be able to quantitatively detect perfusion patterns. Usually, brain activity is normalized to a structure considered unaffected by the disease. Methods: Brain 99mTc-HMPAO SPECT was performed as a method to detect brain perfusion patterns. The patterns of abnormal brain perfusion cannot always be reliably and qualitatively assessed when dealing with rare diseases. Recent advances in SPECT quantification using commercial software have enabled more objective and detailed analysis of brain perfusion. The cerebellum and whole brain were used as the normalization structures and were compared with visual analysis. Results: The quantification analysis performed with whole brain normalization confirmed right parietal lobe hypoperfusion while also detecting statistically significant left-to-right perfusion differences between the temporal lobe and thalamus. Whole brain normalization further described bilateral frontal lobe hyperperfusion, predominantly of the left lobe, and was in accordance with visual analysis. Conclusion: SPECT quantitative brain perfusion analysis, using the whole brain as the normalization structure rather than the cerebellum, in this case, improved confidence in the visual detection of anti-NMDAR encephalitis and provided unexpected solutions to atypical psychiatric dilemmas.
Evenamide Peitl, Vjekoslav; Vlahović, Darko
Archives of Psychiatry Research,
7/2024, Letnik:
60, Številka:
2
Journal Article, Web Resource
Recenzirano
Odprti dostop
In light of the persistent struggles encountered with treatment-resistant schizophrenia (TRS), the pressing urgency remains for the development and implementa- tion of novel therapeutic ...interventions, an essential re- quirement in the realm of health care as a notable por- tion of individuals diagnosed with schizophrenia exhibit minimal positive reactions to antipsychotic medications, even with proper treatment. Evenamide, a newly developed oral compound, selectively inhibits voltage-gated sodium channels (VGSCs) with minimal impact on over 130 other CNS targets. VGSCs are crucial for neuronal excitability and the maintenance of resting potential, playing a vital role in the creation and transmission of action potentials within neurons. Evenamide's primary action involves normalizing glutamate release induced by irregular sodium channel activity without altering baseline glutamate levels, achieved through VGSC inhibition. In animal models of psychosis, evenamide combined with other antipsychotics, including clozapine, showed beneficial outcomes, suggesting potential synergistic mechanisms. Newron’s study 014/015 revealed positive results with evenamide, showing excellent tolerability and minimal adverse effects, with 85 out of 100 patients continuing treatment for 30 weeks. The improvement in TRS symptoms was substantial and increased over time. If corroborated by forthcoming randomized and placebo-controlled trials, evenamide could potentially supplement existing antipsychotics to ameliorate symptoms in TRS cases.
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