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Journal of Clinical Medicine Apr 2024: Schizophrenia, unipolar depression, bipolar disorder, bipolar mania, and bipolar depression are a few of the severe psychiatric diseases that affect millions of...
: Schizophrenia, unipolar depression, bipolar disorder, bipolar mania, and bipolar depression are a few of the severe psychiatric diseases that affect millions of individuals and their overall life quality. This study aimed to look at differences in TGA, TC, HDL, LDL, and FPG levels in people who were going through acute episodes of listed diseases. : A cross-sectional prospective study was carried out in Jordan between January and November of 2023, involving all patients with the aforementioned diseases who attended three psychiatric clinics. This study encompassed results from 1187 patients (women N = 675, 56.87%) who were classified into the following ranges: <25, 25-45, 45-65, and >65. : The average level of LDL was the highest in bipolar depression (112.442 ± 36.178 mg/dL) and the lowest in bipolar mania (111.25 ± 33.14 mg/dL). The average level of HDL was the highest in schizophrenia (58.755 ± 16.198 mg/dL) and the lowest in bipolar depression (45.584 ± 12.128 mg/dL). Both average levels of TC and TGA were the highest in patients with bipolar depression (188.403 ± 37.396 mg/dL and 149.685 ± 96.951 mg/dL, respectively) and the lowest in bipolar mania (164.790 ± 40.488 mg/dL and 100.679 ± 54.337 mg/dL, respectively). The average level of FPG was the highest in unipolar depression (94.00 ± 21.453 mg/dL) and the lowest in bipolar mania (89.492 ± 14.700 mg/dL). : The results confirmed that lipid and glucose abnormalities were more common in people with schizophrenia and mood disorders (unipolar and bipolar).
PubMed: 38731028
DOI: 10.3390/jcm13092499 -
Cureus Apr 2024Background The subgenual cingulate cortex (SGC) has been identified as a key structure within multiple neural circuits whose dysfunction is implicated in the...
Background The subgenual cingulate cortex (SGC) has been identified as a key structure within multiple neural circuits whose dysfunction is implicated in the neurobiology of depression. Deep brain stimulation in the SGC is thought to reduce and normalize local metabolism, causing normalization of circuit behavior and an improvement in depressive symptoms. We hypothesized that nonablative stereotactic radiosurgery (SRS) to the SGC would reduce local metabolism and reduce the severity of depression in patients with treatment-resistant bipolar depression. Methods Under the FDA's Humanitarian Device Exemption program, patients were screened for inclusion and exclusion criteria. Three volunteers meeting the criteria provided informed consent. Bilateral SGC targets were irradiated to a maximum dose of 75 Gy in one fraction. Subjects were followed for one year following the procedure with mood assessments (Hamilton Depression Rating Scale (HDRS), Clinical Global Impression-Improvement, Clinical Global Impression-Severity, and Young Mania Rating Scale), neurocognitive testing (Delis-Kaplan Executive Function System, Wechsler Adult Intelligence Scale III digit span, and California Verbal Learning Test II), and imaging. Further imaging was completed approximately two years after the procedure. Clinical improvement was defined as a ≥50% reduction in HDRS. Results Two of the three subjects showed clinical improvement in depressive symptoms during the follow-up period, while one subject showed no change in symptom severity. One of three subjects was hospitalized for the emergence of an episode of psychotic mania after discontinuing antipsychotic medications against medical advice but promptly recovered with the reinstitution of an antipsychotic. Sequential assessments did not reveal impairment in any cognitive domain assessed. For one of the three subjects, MRI imaging showed evidence of edema at 12 months post-SRS, which resolved at 22 months post-procedure. In a second of three patients, there was evidence of local edema at the target site at long-term follow-up. All imaging changes were asymptomatic. Conclusion Radiosurgical targeting of the SGC may be a noninvasive strategy for the reduction of severe depression in treatment-resistant bipolar disorder. Two out of three patients showed clinical improvement. While these results are promising, further study, including improvements in target selection and dosing considerations, is needed.
PubMed: 38725772
DOI: 10.7759/cureus.57904 -
International Journal of Bipolar... May 2024Red onion husk, a readily available agricultural waste material, contains diverse bioactive compounds with potential health benefits. This study aimed to assess the...
BACKGROUND
Red onion husk, a readily available agricultural waste material, contains diverse bioactive compounds with potential health benefits. This study aimed to assess the safety and therapeutic potential of red onion husk extract in managing manic-like symptoms and associated neurochemical dysfunctions.
METHODS
Acute and repeated oral dose studies were conducted in mice and rats to evaluate the safety profile of the extract. FT-IR analysis identified functional groups in the extract, while GC-MS analysis identified specific bioactive compounds in the flavonoid-rich fraction. A ketamine-induced manic behaviour model in Wistar rats was employed to assess the extract's efficacy in attenuating manic-like symptoms. Behavioural and neurochemical analyses were performed to further investigate the extract's effects.
RESULTS
The extract demonstrated a favourable safety profile in both acute and repeated dose studies. FT-IR analysis revealed a complex mixture of organic compounds, including hydroxyl groups, alkynes/nitriles, aromatic and non-aromatic C = C bonds, amines, and polysaccharides. GC-MS analysis identified 17 bioactive compounds, including five-methyl-2-phenylindolizine, methadone N-oxide, and 3-phenylthiane, S-oxide. Ketamine administration significantly increased oxidative stress markers, TBARS, and suppressed antioxidant enzyme activities (SOD, GPx, CAT) in both the cerebral cortex and hippocampus, alongside elevated acetylcholinesterase (AchE) activity, indicating enhanced neuronal excitability. Pre-treatment with FRF (25 mg/kg) effectively mitigated ketamine-induced oxidative stress, as evidenced by reduced TBARS levels and partially restored SOD and GPx activities. Interestingly, FRF significantly increased CAT activity (p < 0.001), potentially suggesting an additional compensatory mechanism. Notably, FRF pre-treatment also counteracted ketamine-upregulated AchE activity, offering neuroprotection against heightened neuronal excitability.
CONCLUSION
Red onion husk extract exhibits a favourable safety profile and exerts potent antioxidant and neuroprotective effects, possibly through modulating Nrf2 signalling pathways. Its ability to counteract ketamine-induced oxidative stress and neuronal hyperactivity highlights its potential as a complementary therapeutic strategy for managing manic episodes in bipolar disorder. Further research is warranted to elucidate the precise molecular mechanisms underlying FRF's action and explore its clinical efficacy in human studies.
PubMed: 38722415
DOI: 10.1186/s40345-024-00338-7 -
Wellcome Open Research 2024Many people with bipolar disorder have disrupted circadian rhythms. This means that the timing of sleep and wake activities becomes out-of-sync with the standard 24-hour...
Many people with bipolar disorder have disrupted circadian rhythms. This means that the timing of sleep and wake activities becomes out-of-sync with the standard 24-hour cycle. Circadian rhythms are strongly influenced by light levels and previous research suggests that people with bipolar disorder might have a heightened sensitivity to light, causing more circadian rhythm disruption, increasing the potential for triggering a mood switch into mania or depression. Lithium has been in clinical use for over 70 years and is acknowledged to be the most effective long-term treatment for bipolar disorder. Lithium has many reported actions in the body but the precise mechanism of action in bipolar disorder remains an active area of research. Central to this project is recent evidence that lithium may work by stabilising circadian rhythms of mood, cognition and rest/activity. Our primary hypothesis is that people with bipolar disorder have some pathophysiological change at the level of the retina which makes them hypersensitive to the visual and non-visual effects of light, and therefore more susceptible to circadian rhythm dysfunction. We additionally hypothesise that the mood-stabilising medication lithium is effective in bipolar disorder because it reduces this hypersensitivity, making individuals less vulnerable to light-induced circadian disruption. We will recruit 180 participants into the HELIOS-BD study. Over an 18-month period, we will assess visual and non-visual responses to light, as well as retinal microstructure, in people with bipolar disorder compared to healthy controls. Further, we will assess whether individuals with bipolar disorder who are being treated with lithium have less pronounced light responses and attenuated retinal changes compared to individuals with bipolar disorder not being treated with lithium. This study represents a comprehensive investigation of visual and non-visual light responses in a large bipolar disorder population, with great translational potential for patient stratification and treatment innovation.
PubMed: 38716042
DOI: 10.12688/wellcomeopenres.20557.1 -
BMC Psychiatry May 2024Recent evidences have shown sex-differential cognitive deficits in bipolar disorder (BD) and differences in cognitions across BD subtypes. However, the sex-specific...
BACKGROUND
Recent evidences have shown sex-differential cognitive deficits in bipolar disorder (BD) and differences in cognitions across BD subtypes. However, the sex-specific effect on cognitive impairment in BD subtype II (BD-II) remains obscure. The aim of the current study was to examine whether cognitive deficits differ by gender in youth with BD-II depression.
METHOD
This cross-sectional study recruited 125 unmedicated youths with BD-II depression and 140 age-, sex-, and education-matched healthy controls (HCs). The Chinese version of the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) was used to assess cognitive functions. Mood state was assessed using the 24-item Hamilton Depression Rating Scale (24-HDRS) and the Young Mania Rating Scale (YMRS). Multivariate analysis of covariance (MANCOVA) was conducted.
RESULT
Compared with HCs, patients with BD-II depression had lower scores on MCCB composite and its seven cognitive domains (all p < 0.001). After controlling for age and education, MANCOVA revealed significant gender-by-group interaction on attention/vigilance (F = 6.224, df = 1, p = 0.013), verbal learning (F = 9.847, df = 1, p = 0.002), visual learning (F = 4.242, df = 1, p = 0.040), and composite (F = 8.819, df = 1, p = 0.003). Post hoc analyses suggested that males performed worse in the above-mentioned MCCB tests than females in BD-II depression.
CONCLUSION
Our study demonstrated generalized cognitive deficits in unmedicated youths with BD-II depression. Male patients performed more serious cognitive impairment on attention/vigilance, verbal learning, and visual learning compared to female patients.
Topics: Humans; Male; Female; Bipolar Disorder; Cross-Sectional Studies; Adolescent; Cognitive Dysfunction; Sex Factors; Neuropsychological Tests; Young Adult; Psychiatric Status Rating Scales; Cognition
PubMed: 38714952
DOI: 10.1186/s12888-024-05701-7 -
Frontiers in Psychiatry 2024Management of negative symptoms is one of the most challenging and important unmet needs of schizophrenia treatment. Negative symptoms together with positive symptoms... (Review)
Review
Management of negative symptoms is one of the most challenging and important unmet needs of schizophrenia treatment. Negative symptoms together with positive symptoms result in significant psychosocial impairment and poor quality of life. Existing studies on atypical antipsychotics reported limited treatment adherence due to higher prevalence of treatment-emergent adverse events, such as diabetes, weight gain, hyperlipidemia, hyperprolactinemia and hypertension. A compound with greater affinity for dopamine D2/D3 receptors may improve negative symptoms, mood, and cognitive impairment associated with schizophrenia. In 2015, the US FDA has approved cariprazine, a partial D2/D3 agonist for treatment of schizophrenia, mania or mixed episodes. Midlands and Lancashire Commissioning Support Unit, UK (2019) has particularly suggested cariprazine for the treatment of predominant negative symptoms of schizophrenia. India's Central Drugs Standard Control Organization (CDSCO) has approved cariprazine in 2021 for the treatment of schizophrenia, manic or mixed episodes associated with bipolar I disorder. A ten-fold greater affinity for D3 receptors and partial agonism to serotonin receptors, along with longer half-life make cariprazine distinct when compared with other atypical antipsychotics. Cariprazine is also reported to have fewer incidents of metabolic and hormonal adverse events, and has been shown to provide better relapse prevention. Recent evidence indicates promising effect of cariprazine in ameliorating negative symptoms as well as psychotic symptoms in patients with schizophrenia. In addition, improved adherence to treatment (adjunctive/monotherapy) with cariprazine in patients having inadequate response to an ongoing antipsychotic treatment has also been clinically established. This review presents the evidence-based safety and efficacy of cariprazine for treatment of predominant negative symptoms of schizophrenia.
PubMed: 38711874
DOI: 10.3389/fpsyt.2024.1385925 -
BJPsych Open May 2024Identification of the predominant polarity, i.e. hypomanic/manic (mPP) or depressive predominant polarity (dPP), might help clinicians to improve personalised management... (Review)
Review
BACKGROUND
Identification of the predominant polarity, i.e. hypomanic/manic (mPP) or depressive predominant polarity (dPP), might help clinicians to improve personalised management of bipolar disorder.
AIMS
We performed a systematic review and meta-analysis to estimate prevalence and correlates of mPP and dPP in bipolar disorder.
METHOD
The protocol was registered in the Open Science Framework Registries (https://doi.org/10.17605/OSF.IO/8S2HU). We searched main electronic databases up to December 2023 and performed random-effects meta-analyses of weighted prevalence of mPP and dPP. Odds ratios and weighted mean differences (WMDs) were used for relevant correlates.
RESULTS
We included 28 studies, providing information on rates and/or correlates of mPP and dPP. We estimated similar rates of mPP (weighted prevalence = 30.0%, 95% CI: 23.1 to 37.4%) and dPP (weighted prevalence = 28.5%, 95% CI: 23.7 to 33.7%) in bipolar disorder. Younger age (WMD = -3.19, 95% CI: -5.30 to -1.08 years), male gender (odds ratio = 1.39, 95% CI: 1.10 to 1.76), bipolar-I disorder (odds ratio = 4.82, 95% CI: 2.27 to 10.24), psychotic features (odds ratio = 1.56, 95% CI: 1.01 to 2.41), earlier onset (WMD = -1.57, 95% CI: -2.88 to -0.26 years) and manic onset (odds ratio = 13.54, 95% CI: 5.83 to 31.46) were associated with mPP ( < 0.05). Depressive onset (odds ratio = 12.09, 95% CI: 6.38 to 22.90), number of mood episodes (WMD = 0.99, 95% CI: 0.28 to 1.70 episodes), history of suicide attempts (odds ratio = 2.09, 95% CI: 1.49 to 2.93) and being in a relationship (odds ratio = 1.98, 95% CI: 1.22 to 3.22) were associated with dPP ( < 0.05). No differences were estimated for other variables.
CONCLUSIONS
Despite some limitations, our findings support the hypothesis that predominant polarity might be a useful specifier of bipolar disorder. Evidence quality was mixed, considering effects magnitude, consistency, precision and publication bias. Different predominant polarities may identify subgroups of patients with specific clinical characteristics.
PubMed: 38708573
DOI: 10.1192/bjo.2024.51 -
Pharmacological Reviews May 2024Over the last six decades, lithium has been considered the gold standard treatment for the long-term management of bipolar disorder due to its efficacy in preventing... (Review)
Review
Over the last six decades, lithium has been considered the gold standard treatment for the long-term management of bipolar disorder due to its efficacy in preventing both manic and depressive episodes as well as suicidal behaviors. Nevertheless, despite numerous observed effects on various cellular pathways and biologic systems, the precise mechanism through which lithium stabilizes mood remains elusive. Furthermore, there is recent support for the therapeutic potential of lithium in other brain diseases. This review offers a comprehensive examination of contemporary understanding and predominant theories concerning the diverse mechanisms underlying lithium's effects. These findings are based on investigations utilizing cellular and animal models of neurodegenerative and psychiatric disorders. Recent studies have provided additional support for the significance of glycogen synthase kinase-3 (GSK3) inhibition as a crucial mechanism. Furthermore, research has shed more light on the interconnections between GSK3-mediated neuroprotective, antioxidant, and neuroplasticity processes. Moreover, recent advancements in animal and human models have provided valuable insights into how lithium-induced modifications at the homeostatic synaptic plasticity level may play a pivotal role in its clinical effectiveness. We focused on findings from translational studies suggesting that lithium may interface with microRNA expression. Finally, we are exploring the repurposing potential of lithium beyond bipolar disorder. These recent findings on the therapeutic mechanisms of lithium have provided important clues toward developing predictive models of response to lithium treatment and identifying new biologic targets. SIGNIFICANCE STATEMENT: Lithium is the drug of choice for the treatment of bipolar disorder, but its mechanism of action in stabilizing mood remains elusive. This review presents the latest evidence on lithium's various mechanisms of action. Recent evidence has strengthened glycogen synthase kinase-3 (GSK3) inhibition, changes at the level of homeostatic synaptic plasticity, and regulation of microRNA expression as key mechanisms, providing an intriguing perspective that may help bridge the mechanistic gap between molecular functions and its clinical efficacy as a mood stabilizer.
Topics: Humans; Animals; Lithium Compounds; Antimanic Agents; Bipolar Disorder; Neuronal Plasticity; Glycogen Synthase Kinase 3
PubMed: 38697859
DOI: 10.1124/pharmrev.120.000007 -
International Journal of Bipolar... May 2024This is an overview of recent advances on predominant polarity conceptualization in bipolar disorder (BD). Current evidence on its operationalized definitions, possible...
This is an overview of recent advances on predominant polarity conceptualization in bipolar disorder (BD). Current evidence on its operationalized definitions, possible contextualization within the affective spectrum, along with its epidemiological impact, and treatment implications, are summarized. Predominant polarity identifies three subgroups of patients with BD according to their mood recurrencies: (i) those with depressive or (ii) manic predominance as well as (iii) patients without any preponderance ('nuclear' type). A predominant polarity can be identified in approximately half of patients, with similar rates for depressive and manic predominance. Different factors may influence the predominant polarity, including affective temperaments. More generally, affective disorders should be considered as existing on a spectrum ranging from depressive to manic features, also accounting for disorders with 'ultrapredominant' polarity, i.e., unipolar depression and mania. While mixed findings emerge on its utility in clinical practice, it is likely that the construct of predominant polarity, in place of conventional differentiation between BD-I and BD-II, may be useful to clarify the natural history of the disorder and select the most appropriate interventions. The conceptualization of predominant polarity seems to reconcile previous theoretical views of both BD and affective spectrum into a novel perspective. It may provide useful information to clinicians for the early identification of possible trajectories of BD and thus guide them when selecting interventions for maintenance treatment. However, further research is needed to clarify the specific role of predominant polarity as a key determinant of BD course, outcome, and treatment response.
PubMed: 38696069
DOI: 10.1186/s40345-024-00336-9 -
Archive of Clinical Cases 2024Mixed depressive states are defined by the co-presence of depressive and manic symptoms. They represent extremely variable conditions from the point of view of clinical...
Mixed depressive states are defined by the co-presence of depressive and manic symptoms. They represent extremely variable conditions from the point of view of clinical expressiveness and are difficult to recognize, ranging from clear schizophrenic-like psychoses and pseudodemented pictures to subsyndromal psychopathology. At the basis of the extreme variability of depressive pictures with mixed features are the different combinations that depressive and manic symptoms can assume. Furthermore, the intensity of depressive symptoms and manic symptoms, combined, can be variable, a factor that contributes to making the picture even more variable. Each form of mixed depressive state therefore presents its own specific symptomatic characteristics and specific difficulties in differential diagnosis and each form requires a different therapeutic strategy. In this work we have distinguished four possible specific subtypes of mixed depressive states, describing their specific clinical presentation and the therapeutic options most supported by the literature with the aim of contributing to a better recognition of mixed depressive states, to avoid incorrect diagnoses at patient and treatments that are useless if not worsening.
PubMed: 38689821
DOI: 10.22551/2024.42.1101.10282