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British Journal of Pharmacology Sep 2022Rats emit 50-kHz ultrasonic vocalizations (USV) in appetitive situations, reflecting a positive affective state. Particularly high rates of 50-kHz USV are elicited by... (Review)
Review
Rats emit 50-kHz ultrasonic vocalizations (USV) in appetitive situations, reflecting a positive affective state. Particularly high rates of 50-kHz USV are elicited by the psychostimulant d-amphetamine. Exaggerated 50-kHz USV emission evoked by d-amphetamine is modulated by dopamine, noradrenaline and 5-hydroxytyrptamine receptor ligands and inhibited by the mood stabilizer lithium, the gold standard anti-manic drug for treating bipolar disorder. This indicates that exaggerated 50-kHz USV emission can serve as a reliable and valid measure for assessing mania-like elevated mood in rats with sufficient translational power for gaining a better understanding of relevant pathophysiological mechanisms and the identification of new therapeutic targets. The improved capacity to study the effects of anti-manic pharmacological interventions on a broader range of behaviours by including exaggerated 50-kHz USV emission as preclinical outcome measure complementary to locomotor hyperactivity will refine rodent models for mania. LINKED ARTICLES: This article is part of a themed issue on New discoveries and perspectives in mental and pain disorders. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.17/issuetoc.
Topics: Amphetamine; Animals; Antimanic Agents; Dextroamphetamine; Mania; Rats; Ultrasonics; Vocalization, Animal
PubMed: 33830495
DOI: 10.1111/bph.15487 -
Current Neuropharmacology Apr 2017Athanasios Koukopoulos provided a radical model for understanding depressive and manic conditions. (Review)
Review
BACKGROUND
Athanasios Koukopoulos provided a radical model for understanding depressive and manic conditions.
OBJECTIVE
To review, explain, and analyze Koukopoulos' concept of the primacy of mania, with special attention to the role of antidepressants.
METHOD
A conceptual review of Koukopoulos' writings and lectures on this topic is given.
RESULTS
Koukopoulos held that depressive states are caused by manic states; the former do not occur without the latter. The most common scenario of the inseparability of depressive and manic symptoms occurs in mixed states, which we estimate to represent about one-half of all depressive episodes in all patients (not just bipolar illness). In a review of the empirical evidence for this topic, we conclude that empirical evidence exists to support the primary of mania thesis in almost 80% of depressed patients. Since antidepressants worsen mania, they would be expected to worsen depression as well in this model. We provide evidence that supports this view in most persons with depressive states.
CONCLUSION
Koukopoulos' model of affective illness is one where manic states are the primary pathology, and depressive conditions are a secondary consequence. Hence treatment of depression with antidepressants would be less effective than treatment with mood stabilizers, since treating an effect is less successful than treating its cause. This approach would reverse current assumptions in psychiatry.
Topics: Antidepressive Agents; Bipolar Disorder; Diagnosis, Differential; History, 20th Century; History, 21st Century; Humans; Psychiatric Status Rating Scales; Psychiatry
PubMed: 28503112
DOI: 10.2174/1570159X14666160621113432 -
European Neuropsychopharmacology : the... Aug 2023The present systematic review was aimed at critically summarizing the evidence about treatment-emergent manic/hypomanic and depressive switches during the course of... (Review)
Review
A systematic review of manic/hypomanic and depressive switches in patients with bipolar disorder in naturalistic settings: The role of antidepressant and antipsychotic drugs.
The present systematic review was aimed at critically summarizing the evidence about treatment-emergent manic/hypomanic and depressive switches during the course of bipolar disorder (BD). A systematic search of the MEDLINE, EMBASE, CINAHL, Web of Science, and PsycInfo electronic databases was conducted until March 24th, 2021, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Observational studies clearly reporting data regarding the prevalence of treatment-emergent mood switches in patients with BD were considered for inclusion. Thirty-two original studies met the inclusion criteria. In the majority of cases, manic switches were analyzed; only 3 papers investigated depressive switches in type I BD. Treatment-emergent mania/hypomania in BD subjects ranged from 17.3% to 48.8% and was more frequent with antidepressant monotherapy compared to combination treatment with mood stabilizers, especially lithium, or second-generation antipsychotics. A higher likelihood of mood switch has been reported with tricyclics and a lower rate with bupropion. Depressive switches were detected in 5-16% of type I BD subjects and were associated with first-generation antipsychotic use, the concomitant use of first- and second-generation antipsychotics, and benzodiazepines. The included studies presented considerable methodological heterogeneity, small sample sizes and comparability flaws. In conclusion, many studies, although heterogeneous and partly discordant, have been conducted on manic/hypomanic switches, whereas depressive switches during treatment with antipsychotics are poorly investigated. In BD subjects, both antidepressant and antipsychotic medications seems to play a role in the occurrence of mood switches, although the effects of different pharmacological compounds have yet to be fully investigated.
Topics: Humans; Bipolar Disorder; Antipsychotic Agents; Mania; Antidepressive Agents; Lithium
PubMed: 37119556
DOI: 10.1016/j.euroneuro.2023.04.013 -
International Clinical... Nov 2022Inflammatory processes are associated with mood disorders, but data on pediatric patients are scarce. The aim of this study was to investigate a possible association...
Inflammatory processes are associated with mood disorders, but data on pediatric patients are scarce. The aim of this study was to investigate a possible association between elevated neutrophil/lymphocyte ratio (NLR) - a marker of inflammation and mood polarity (manic/depressed) in adolescents, admitted between 2010 and 2015 due to a mood disorder episode and to an adolescent inpatient ward. Electronic medical records of 305 patients (aged 10-19 years, 60.6% males) admitted during the study period due to a mood disorder episode were reviewed. Of these, 63 were diagnosed with manic episodes and 242 with depressive episodes. Multivariate analyses were used to compare NLR between and within the two groups, covarying for age, sex, and antipsychotic use. NLR was significantly higher in the manic episode group compared with the depression one. Moreover, in inpatients with multiple hospitalizations, the NLR was higher during their manic episodes than that during their nonmanic states. These results suggest that, as has been reported in adults with bipolar disorder, inflammatory mechanisms may be involved in adolescents' mood disorders as well, particularly in the manic episodes. Thus, clinicians may consider adding anti-inflammatories as part of the treatment of these patients.
Topics: Adolescent; Adult; Antipsychotic Agents; Child; Female; Hospitalization; Humans; Inpatients; Lymphocytes; Male; Mania; Neutrophils; Psychiatric Department, Hospital
PubMed: 35833290
DOI: 10.1097/YIC.0000000000000412 -
Brain and Behavior Mar 2021The aim of this study is to explore mania as a network of its symptoms, inspired by the network approach to mental disorders.
OBJECTIVES
The aim of this study is to explore mania as a network of its symptoms, inspired by the network approach to mental disorders.
METHODS
Network structures of both cross-sectional and temporal effects were measured at three time points (admission, middle of hospital stay, and discharge) in a sample of 100 involuntarily committed patients diagnosed with bipolar I disorder with severe manic features and hospitalized in a specialized psychiatric ward.
RESULTS
Elevated mood is the most interconnected symptom in the network on admission, while aggressive behavior and irritability are highly predictive of each other, as well as language-thought disorder and "content" (the presence of abnormal ideas or delusions). Elevated mood is influenced by many symptoms in the temporal network.
CONCLUSIONS
The investigation of manic symptoms with network analysis allows for identifying important symptoms that are better connected to other symptoms at a given moment and over time. The connectivity of the manic symptoms evolves over time. Central symptoms could be considered as targets for clinical intervention when treating severe mania.
Topics: Bipolar Disorder; Cross-Sectional Studies; Humans; Psychiatric Status Rating Scales
PubMed: 33452874
DOI: 10.1002/brb3.2010 -
Translational Psychiatry Apr 2022Manic episodes are a defining, frequent and dramatically disabling occurrence in the course of Bipolar Disorder type I. Current pharmacotherapy of mania lists a good... (Review)
Review
Manic episodes are a defining, frequent and dramatically disabling occurrence in the course of Bipolar Disorder type I. Current pharmacotherapy of mania lists a good number of agents, but differences in efficacy and safety profiles among these agents must be considered in order to tailor personalized therapies, especially when the long-term course of the illness is considered. There is wide room and need to ameliorate current pharmacological approaches to mania, but ongoing pharmacological research on the topic is scant. In this work we try to critically assess clinical factors and patients' characteristics that may influence the treatment choice for manic episodes. In addition, we conduct a narrative review on experimental pharmacology of bipolar mania and psychotic disorders, presenting a critical overview on agents which could represent treatment alternatives for a manic episode in the next future. Results show limited novel or ongoing research on agents acting as mood stabilizers (Ebselen, Valnoctamide and Eslicarbazepine did not reach statistical significance in demonstrating antimanic efficacy). As for the emerging experimental antipsychotic, some of them (including KarXT, SEP-363856, RO6889450, ALKS3831) have demonstrated good antipsychotic efficacy and a favorable safety profile, but little is known about their use in patients with bipolar disorder and specifically designed trials are needed. Lastly, some benefits for the treatment of mania could be expected to come in the next future from non-mood stabilizers/non-antipsychotic agents (especially PKC inhibitors like Endoxifen): long-term trials are needed to confirm positive results in terms of long-term efficacy and safety.
Topics: Anticonvulsants; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Humans; Mania; Psychotic Disorders
PubMed: 35461339
DOI: 10.1038/s41398-022-01928-8 -
Current Neuropharmacology Apr 2017Pediatric Bipolar Disorder (BD) is a highly morbid pediatric psychiatric disease, consistently associated with family psychiatric history of mood disorders and... (Review)
Review
Pediatric Bipolar Disorder (BD) is a highly morbid pediatric psychiatric disease, consistently associated with family psychiatric history of mood disorders and associated with high levels of morbidity and disability and with a great risk of suicide. While there is a general consensus on the symptomatology of depression in childhood, the phenomenology of pediatric mania is still highly debated and the course and long-term outcome of pediatric BD still need to be clarified. We reviewed the available studies on the phenomenology of pediatric mania with the aim of summarizing the prevalence, demographics, clinical correlates and course of these two types of pediatric mania. Eighteen studies reported the number of subjects presenting with either irritable or elated mood during mania. Irritability has been reported to be the most frequent clinical feature of pediatric mania reaching a sensitivity of 95-100% in several samples. Only half the studies reviewed reported on number of episodes or cycling patterns and the described course was mostly chronic and ultra-rapid whereas the classical episodic presentation was less common. Few long-term outcome studies have reported a diagnostic stability of mania from childhood to young adult age. Future research should focus on the heterogeneity of irritability aiming at differentiating distinct subtypes of pediatric psychiatric disorders with distinct phenomenology, course, outcome and biomarkers. Longitudinal studies of samples attending to mood presentation, irritable versus elated, and course, chronic versus episodic, may help clarify whether these are meaningful distinctions in the course, treatment and outcome of pediatric onset bipolar disorder.
Topics: Adolescent; Bipolar Disorder; Child; Diagnosis, Differential; Euphoria; Humans; Irritable Mood; Suicide
PubMed: 28503110
DOI: 10.2174/1570159X14666160607100403 -
Journal of Affective Disorders Feb 2021It has not been established that suicide risk with mixed symptoms is any greater than the depressive component or if there is synergy between depressive and manic...
Moderators of the association between depressive, manic, and mixed mood symptoms and suicidal ideation and behavior: An analysis of the National Network of Depression Centers Mood Outcomes Program.
BACKGROUND
It has not been established that suicide risk with mixed symptoms is any greater than the depressive component or if there is synergy between depressive and manic symptoms in conveying suicide risk.
METHODS
The National Network of Depression Centers Mood Outcomes Program collected data from measurement-based care for 17,179 visits from 6,105 unique individuals with clinically diagnosed mood disorders (998 bipolar disorder, 5,117 major depression). The Patient Health Questionaire-8 (PHQ-8) captured depressive symptoms and the Altman Self-Rating Mania scale (ASRM) measured hypomanic/manic symptoms. Generalized linear mixed models assessed associations between depressive symptoms, manic symptoms, and their interaction (to test for synergistic effects of mixed symptoms) on the primary outcome of suicidal ideation or behavior (secondarily suicidal behavior only) from the Columbia-Suicide Severity Rating Scale (C-SSRS). Moderation was assessed.
RESULTS
PHQ-8 scores were strongly associated with suicide-related outcomes across diagnoses. ASRM scores showed no association with suicidal ideation/behavior in bipolar disorder and an inverse association in major depression. There was no evidence of synergy between depressive and manic symptoms. There was no moderation by sex, race, or mood disorder polarity. Those over 55 years of age showed a protective effect of manic symptoms, which was lost when depressive symptoms were also present (mixed symptoms).
DISCUSSION
Mixed depressive and manic symptoms convey no excess risk of suicidal ideation or behavior beyond the risk conveyed by the depressive symptoms alone. Depressive symptoms are strongly linked to suicidal ideation and suicidal behavior and represent an important and potentially modifiable risk factor for suicide.
Topics: Affect; Bipolar Disorder; Depression; Humans; Suicidal Ideation; Suicide
PubMed: 33234283
DOI: 10.1016/j.jad.2020.11.101 -
The International Journal of... Oct 2022Existing meta-analytic evidence on bipolar mania treatment has revealed that augmentation therapy (AUG) with antipsychotics and mood stabilizers is more effective than... (Meta-Analysis)
Meta-Analysis
Mood Stabilizers and Antipsychotics for Acute Mania: Systematic Review and Meta-Analysis of Augmentation Therapy vs Monotherapy From the Perspective of Time to the Onset of Treatment Effects.
BACKGROUND
Existing meta-analytic evidence on bipolar mania treatment has revealed that augmentation therapy (AUG) with antipsychotics and mood stabilizers is more effective than monotherapy. However, the speed of the onset of treatment effects and subsequent changes in risk/benefit are unclear.
METHODS
We searched the Cochrane CENTRAL, MEDLINE, and EMBASE databases until January 2021. Our primary outcomes were response and tolerability. We set 3 time points: 1, 3, and 6 weeks after randomization.
RESULTS
Seventeen studies compared AUG therapy and MS monotherapy (comparison 1), and 8 studies compared AUG therapy and antipsychotics monotherapy (comparison 2). In comparison 1, AUG therapy resulted in significantly more responses than monotherapy, with an odds ratio of 1.45 (95% confidence interval [CI]: 1.17 to 1.80) at 3 weeks and 1.59 (95% CI: 1.28 to 1.99) at 6 weeks. Significant improvement was observed in the first week with a standardized mean difference of -0.25 (95% CI: -0.38 to -0.12). In comparison 2, AUG therapy was significantly more effective than monotherapy, with an odds ratio of 1.73 (95% CI: 1.25 to 2.40) at 3 weeks and 1.74 (95% CI: 1.11 to 2.73) at 6 weeks. Significant improvement was observed in the first week with an standardized mean difference of -0.23 (95% CI: -0.39 to -0.07). Regarding tolerability, there was no significant difference between AUG therapy and monotherapy at 3 and 6 weeks in both comparisons.
CONCLUSIONS
Early AUG therapy should be considered, as it has shown efficacy from weeks 1 to 6, although attention to side effects is necessary for acute mania treatment.
Topics: Humans; Antipsychotic Agents; Mania; Bipolar Disorder; Antimanic Agents; Anticonvulsants
PubMed: 35932466
DOI: 10.1093/ijnp/pyac050 -
BMC Women's Health Mar 2022Despite high co-morbidity between premenstrual dysphoric disorder and mood disorders, there is a gap of research-based tools to monitor concurrent premenstrual and mood...
BACKGROUND
Despite high co-morbidity between premenstrual dysphoric disorder and mood disorders, there is a gap of research-based tools to monitor concurrent premenstrual and mood symptoms. In this study, we developed a new DSM-5-based questionnaire to prospectively monitor concurrent premenstrual and mood symptoms.
METHODS
Fifty-two females with bipolar or major depressive disorder, ages 16-45, were enrolled in the study. Participants completed two months of prospective symptom charting including the McMaster Premenstrual and Mood Symptom Scale (MAC-PMSS) and the Daily Record of Severity of Problems (DRSP). At the end of the prospective charting, participants also completed the Montgomery-Åsberg Depression Rating Scale (MADRS), Hamilton Depression Rating Scale (HDRS) and the Young Mania Rating Scale (YMRS). The MAC-PMSS was correlated with the DRSP, MADRS, HDRS and YMRS.
RESULTS
All individual items of the MAC-PMSS correlated strongly with the individual DRSP scores (all p < 0.001). The mood section of the MAC-PMSS also significantly correlated with MADRS (r = 0.572; p < 0.01), HDRS (r = 0.555; p < 0.01) and YMRS scores (r = 0.456; p < 0.01).
CONCLUSIONS
The MAC-PMSS is a reliable to tool to measure concurrent mood and premenstrual symptoms in women with mood disorders.
Topics: Adolescent; Adult; Affect; Depressive Disorder, Major; Female; Humans; Middle Aged; Prospective Studies; Surveys and Questionnaires; Young Adult
PubMed: 35354450
DOI: 10.1186/s12905-022-01678-1