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The Journal of Neuropsychiatry and... 2020Previous studies have documented manic and hypomanic symptoms in behavioral variant frontotemporal dementia (bvFTD), suggesting a relationship between bipolar disorder... (Review)
Review
OBJECTIVE
Previous studies have documented manic and hypomanic symptoms in behavioral variant frontotemporal dementia (bvFTD), suggesting a relationship between bipolar disorder and bvFTD.
METHODS
The investigators conducted a literature review as well as a review of the psychiatric histories of 137 patients with bvFTD, and patients with a prior diagnosis of bipolar disorder were identified. The clinical characteristics of patients' bipolar disorder diagnosis, family history, features of bvFTD, and results from fluorodeoxyglucose positron emission tomography (FDG-PET), as well as autopsy findings, were evaluated.
RESULTS
Among the 137 patients, 14 (10.2%) had a psychiatric diagnosis of bipolar disorder, eight of whom met criteria for bipolar disorder (type I, N=6; type II, N=2) 6-12 years preceding onset of classic symptoms of progressive bvFTD. Seven of the eight patients with bipolar disorder had a family history of mood disorders, four had bitemporal predominant hypometabolism on FDG-PET, and two had a tauopathy involving temporal lobes on autopsy. Three additional patients with late-onset bipolar I disorder proved to have a nonprogressive disorder mimicking bvFTD. The remaining three patients with bvFTD had prior psychiatric symptoms that did not meet criteria for a diagnosis of bipolar disorder. The literature review and the findings for one patient further suggested a shared genetic mutation in some patients.
CONCLUSIONS
Manic or hypomanic episodes years before other symptoms of bvFTD may be a prodrome of this dementia, possibly indicating anterior temporal involvement in bvFTD. Other patients with late-onset bipolar disorder exhibit the nonprogressive frontotemporal dementia phenocopy syndrome. Finally, a few patients with bvFTD have a genetic predisposition for both disorders.
Topics: Adult; Age of Onset; Aged; Bipolar Disorder; Female; Frontotemporal Dementia; Humans; Magnetic Resonance Imaging; Male; Mania; Middle Aged; Positron-Emission Tomography; Prodromal Symptoms; Retrospective Studies
PubMed: 32498603
DOI: 10.1176/appi.neuropsych.20010003 -
BMC Psychiatry May 2022Pediatric bipolar disorder is a highly prevalent and morbid disorder and is considered a prevalent public health concern. Currently approved treatments often pose the... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Pediatric bipolar disorder is a highly prevalent and morbid disorder and is considered a prevalent public health concern. Currently approved treatments often pose the risk of serious side effects. Therefore, this study assessed the efficacy and tolerability of N-acetylcysteine (NAC), in children and adolescents with bipolar spectrum disorder.
METHODS
We conducted a 12-week open-label trial of NAC for treatment of mania and hypomania in children and adolescents ages 5-17 with bipolar spectrum disorder including participants with full and subthreshold manic symptoms, accepting those with and without mixed states with co-occurring depression, and Young Mania Rating Scale scores ≥ 20 and < 40. Symptoms of mania and depression were assessed using the Young Mania Rating Scale (YMRS), Hamilton Depression Rating Scale (HDRS), Children's Depression Rating Scale (CDRS), and Clinical Global Impression (CGI) Severity (CGI-S) and Improvement (CGI-I) scales for mania and depression.
RESULTS
This study had a high drop-out rate with only 53% completing all 12 weeks. There was a significant reduction in YMRS, HDRS, and CDRS mean scores from baseline to endpoint. Of the 24 exposed participants, 54% had an anti-manic response measured by a reduction in YMRS ≥ 30% and 46% had a CGI-I mania score ≤ 2 at endpoint. Additionally, 62% of participants had an anti-depressive response measured by a reduction in HDRS ≥ 30%, 31% had an anti-depressive response measured by a reduction in CDRS ≥ 30%, and 38% had a CGI-I depression score ≤ 2 at endpoint.
CONCLUSIONS
These pilot open-label findings in a small sample provide preliminary data supporting the tolerability and safety of NAC in a pediatric population. The findings of this pilot scale study indicating improvement in mania and depression are promising, but require replication with a monotherapy randomized placebo controlled clinical trial and larger sample.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02357290 . First Registration 06/02/2015.
Topics: Acetylcysteine; Adolescent; Antimanic Agents; Bipolar Disorder; Child; Child, Preschool; Humans; Mania; Pilot Projects
PubMed: 35505312
DOI: 10.1186/s12888-022-03943-x -
Current Neuropharmacology Apr 2017Athanasios Koukopoulos proposed the primacy of mania hypothesis (PoM) in a 2006 book chapter and later, in two peer-reviewed papers with Nassir Ghaemi and other... (Review)
Review
BACKGROUND
Athanasios Koukopoulos proposed the primacy of mania hypothesis (PoM) in a 2006 book chapter and later, in two peer-reviewed papers with Nassir Ghaemi and other collaborators. This hypothesis supports that in bipolar disorder, mania leads to depression, while depression does not lead to mania.
OBJECTIVE
To identify evidence in literature that supports or falsifies this hypothesis.
METHOD
We searched the medical literature (PubMed, Embase, PsycINFO, and the Cochrane Library) for peer-reviewed papers on the primacy of mania, the default mode function of the brain in normal people and in bipolar disorder patients, and on illusion superiority until 6 June, 2016. Papers resulting from searches were considered for appropriateness to our objective. We adopted the PRISMA method for our review. The search for consistency with PoM was filtered through the neurobiological results of superiority illusion studies.
RESULTS
Out of a grand total of 139 records, 59 were included in our analysis. Of these, 36 were of uncertain value as to the primacy of mania hypothesis, 22 favoured it, and 1 was contrary, but the latter pooled patients in their manic and depressive phases, so to invalidate possible conclusions about its consistency with regard to PoM. All considered studies were not focused on PoM or superiority illusion, hence most of their results were, as expected, unrelated to the circuitry involved in superiority illusion. A considerable amount of evidence is consistent with the hypothesis, although indirectly so.
LIMITATIONS
Only few studies compared manic with depressive phases, with the majority including patients in euthymia.
CONCLUSION
It is possible that humans have a natural tendency for elation/optimism and positive self-consideration, that are more akin to mania; the depressive state could be a consequence of frustrated or unsustainable mania. This would be consistent with PoM.
Topics: Bipolar Disorder; Brain; Humans; Magnetic Resonance Imaging; Models, Neurological; Rest
PubMed: 28503105
DOI: 10.2174/1570159X14666160708231216 -
Bipolar Disorders May 2021First, to investigate whether specific manic symptoms in preschool predict manic symptom severity in adolescence. Second, to investigate the interaction between family...
OBJECTIVES
First, to investigate whether specific manic symptoms in preschool predict manic symptom severity in adolescence. Second, to investigate the interaction between family history (FH) of bipolar disorder (BP) and preschool manic symptoms in predicting later adolescent manic symptom severity.
METHODS
This analysis utilized data from the Preschool Depression Study (PDS) which followed 306 preschoolers aged 3-6 years over time since 2003. Only subjects who had data both at baseline (age 3-6 years) and at or after age 12 were included (n = 122). Baseline manic symptom severity scores and diagnoses were assessed by the Preschool Age Psychiatric Assessment (PAPA). Manic symptoms severity at age ≥12 was assessed by the Kiddie Mania Rating Scale (KMRS). FH were ascertained by Family Interview for Genetic Studies (FIGS). Multilevel models of KMRS total score at age ≥12 by preschool mania symptoms with gender, baseline age, baseline ADHD, as well as baseline MDD diagnosis as covariates, and false discovery rate correction were used in statistical analysis.
RESULTS
Hypertalkativity, flight of ideas, uninhibited gregariousness, decreased need for sleep (DNFS), and increased motor pressure/ motor activity/ energy in preschool were associated with increased KMRS score at age ≥12. Racing thoughts, inappropriate laughing, and DNFS in early childhood were associated with higher manic symptoms in adolescence in subjects with FH of BP compared to those without FH.
CONCLUSION
The longitudinal clinical importance of displaying manic symptoms (racing thoughts, inappropriate laughing, and DNFS) in early childhood varies by FH. Among the aforementioned symptoms, DNFS was a robust predictor of later manic symptoms. Assessing FH of BP is very important in clinical risk prediction from early childhood.
Topics: Adolescent; Bipolar Disorder; Child; Child, Preschool; Humans; Psychiatric Status Rating Scales; Psychomotor Agitation
PubMed: 33450097
DOI: 10.1111/bdi.13046 -
Neuropsychopharmacology : Official... Mar 2023Disruptions in the limbic system, and in emotion regulation circuitry that supports affect modulation, have been reported during acute manic episodes of bipolar disorder... (Randomized Controlled Trial)
Randomized Controlled Trial
Effects of short-term quetiapine and lithium therapy for acute manic or mixed episodes on the limbic system and emotion regulation circuitry in youth with bipolar disorder.
Disruptions in the limbic system, and in emotion regulation circuitry that supports affect modulation, have been reported during acute manic episodes of bipolar disorder (BD). The impact of pharmacological treatment on these deficits, especially in youth, remains poorly characterized. 107 youths with acute manic or mixed episodes of bipolar I disorder and 60 group-matched healthy controls were recruited. Youth with bipolar disorder were randomized to double-blind treatment with quetiapine or lithium and assessed weekly. Task-based fMRI studies were performed using an identical pairs continuous performance task (CPT-IP) at pre-treatment baseline and post-treatment weeks one and six. Region of interest analyses focused on the limbic system and ventral PFC - basal ganglia - thalamocortical loop structures known to be involved in emotion regulation. Changes in regional activation were compared between the two treatment groups, and pretreatment regional activation was used to predict treatment outcome. Mania treatment scores improved more rapidly in the quetiapine than lithium treated group, as did significant normalization of neural activation toward that of healthy individuals in left amygdala (p = 0.007), right putamen (p < 0.001), and right globus pallidus (p = 0.003). Activation changes in the right putamen were correlated with reduction of mania symptoms. The limbic and emotion regulation system activation at baseline and week one predicted treatment outcome in youth with bipolar disorder with significant accuracy (up to 87.5%). Our findings document more rapid functional brain changes associated with quetiapine than lithium treatment in youth with bipolar disorder, with most notable changes in the limbic system and emotion regulation circuitry. Pretreatment alterations in these regions predicted treatment response. These findings advance understanding of regional brain alterations in youth with bipolar disorder, and show that fMRI data can predict treatment outcome before it can be determined clinically, highlighting the potential utility of fMRI biomarkers for early prediction of treatment outcomes in bipolar disorder.Clinical Trials Registration: Name: Multimodal Neuroimaging of Treatment Effects in Adolescent Mania. URL: https://clinicaltrials.gov/ . Registration number: NCT00893581.
Topics: Adolescent; Humans; Amygdala; Antipsychotic Agents; Bipolar Disorder; Emotional Regulation; Lithium; Lithium Compounds; Magnetic Resonance Imaging; Mania; Quetiapine Fumarate; Double-Blind Method
PubMed: 36229596
DOI: 10.1038/s41386-022-01463-6 -
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 -
International Journal of Bipolar... Dec 2017In the last two decades, there has been a significant increase in the diagnosis of Bipolar Disorder (BD) in children. The notion of prepubertal onsets of BD is not... (Review)
Review
A systematic review of the frequency and severity of manic symptoms reported in studies that compare phenomenology across children, adolescents and adults with bipolar disorders.
BACKGROUND
In the last two decades, there has been a significant increase in the diagnosis of Bipolar Disorder (BD) in children. The notion of prepubertal onsets of BD is not without controversy, with researchers debating whether paediatric cases have a distinct symptom profile or follow a different illness trajectory from other forms of BD. The latter issue is difficult to address without long-term prospective follow-up studies. However, in the interim, it is useful to consider the phenomenology observed in groups of cases with different ages of onset and particularly to compare manic symptoms in children diagnosed with BD compared to cases presenting with BD in adolescence and adulthood. This review systematically explores the phenomenology of manic or hypomanic episodes in groups defined by age at onset of BD (children, adolescents and adults; or combined age groups e.g. children and adolescents versus adults).
METHODS
Literature reviews of PubMed and Scopus were conducted to identify publications which directly compared the frequency or severity of manic symptoms in individuals with BD presenting with a first episode of mania in childhood, adolescence or adulthood.
RESULTS
Of 304 studies identified, 55 texts warranted detailed review, but only nine studies met eligibility criteria for inclusion. Comparison of manic symptoms across age groups suggested that irritability is a key feature of BD with an onset in childhood, activity is the most prominent in adolescent-onset BD and pressure of speech is more characteristic of adult-onset BD. However, none of the eligible studies made a direct comparison of phenomenology in children versus adults. Assessment procedures varied in quality and undermined the reliability of cross-study comparisons. Other limitations were: the scarcity of comparative studies, the geographic bias (most studies originated in the USA), the failure to fully consider the impact of psychiatric comorbidities on recorded symptoms and methodological heterogeneity.
CONCLUSIONS
Despite frequent discussion of similarities and differences in phenomenology of mania presenting in different age groups, systematic research is lacking and studies are still required to reliably establish whether the frequency and severity of manic symptoms varies. Such information has implications for clinical practice and the classification of mental disorders.
PubMed: 28155204
DOI: 10.1186/s40345-017-0071-y -
World Journal of Psychiatry Dec 2014We review preclinical and clinical evidences strongly suggesting that memantine, an old drug currently approved for Alzheimer's dementia, is an effective treatment for... (Review)
Review
UNLABELLED
We review preclinical and clinical evidences strongly suggesting that memantine, an old drug currently approved for Alzheimer's dementia, is an effective treatment for acute mania and for the prevention of manic/hypomanic and depressive recurrences of manic-depressive illness. Lithium remains the first line for the treatment and prophylaxis of bipolar disorders, but currently available treatment alternatives for lithium resistant patients are of limited and/or questionable efficacy. Thus, research and development of more effective mood stabilizer drugs is a leading challenge for modern psychopharmacology. We have demonstrated that 21 d administration of imipramine causes a behavioural syndrome similar to a cycle of bipolar disorder, i.e., a mania followed by a depression, in rats. Indeed, such treatment causes a behavioural supersensitivity to dopamine D2 receptor agonists associated with an increase sexual activity and aggressivity (mania). The dopamine receptor sensitization is followed, after imipramine discontinuation, by an opposite phenomenon (dopamine receptor desensitization) and an increased immobility time (depression) in the forced swimming test of depression. Memantine blocks the development of the supersensitivity and the ensuing desensitization associated with the depressive like behavior. On the basis of these observations we have suggested the use of memantine in the treatment of mania and in the prophylaxis of bipolar disorders. To test this hypothesis we performed several naturalistic studies that showed an acute antimanic effect and a long-lasting and progressive mood-stabilizing action (at least 3 years), without clinically relevant side effects. To confirm the observations of our naturalistic trials we are now performing a randomized controlled clinical trial. Finally we described the studies reporting the efficacy of memantine in manic-like symptoms occurring in psychiatric disorders other than bipolar.
LIMITATIONS
A randomized controlled clinical trial is needed to confirm our naturalistic observations.
CONCLUSION
We believe that this review presents enough pharmacological and clinical information to consider the administration of memantine in the treatment of bipolar disorders that no respond to standard mood stabilizers.
PubMed: 25540723
DOI: 10.5498/wjp.v4.i4.80 -
BMJ Mental Health Feb 2023Are antipsychotic dose equivalents between acute mania and schizophrenia the same? (Meta-Analysis)
Meta-Analysis
QUESTION
Are antipsychotic dose equivalents between acute mania and schizophrenia the same?
STUDY SELECTION AND ANALYSIS
Six databases were systematically searched (from inception to 17 September 2022) to identify blinded randomised controlled trials (RCTs) that used a flexible-dose oral antipsychotic drug for patients with acute mania. The mean and SD of the effective dose and the pre-post changes in manic symptoms were extracted. A network meta-analysis (NMA) under a frequentist framework was performed to examine the comparative efficacy between the antipsychotics. A classic mean dose method (sample size weighted) was used to calculate each antipsychotic dose equivalent to 1 mg/day olanzapine for acute mania. The antipsychotic dose equivalents of acute mania were compared with published data for schizophrenia.
FINDINGS
We included 42 RCTs which enrolled 11 396 participants with acute mania. The NMA showed that risperidone was superior to olanzapine (reported standardised mean difference: -022, 95% CI -0.41 to -0.02), while brexpiprazole was inferior to olanzapine (standardised mean difference: 0.36, 95% CI 0.08 to 0.64). The dose equivalents to olanzapine (with SD) were 0.68 (0.23) for haloperidol, 0.32 (0.07) for risperidone, 0.60 (0.11) for paliperidone, 8.00 (1.41) for ziprasidone, 41.46 (5.98) for quetiapine, 1.65 (0.32) for aripiprazole, 1.23 (0.20) for asenapine, 0.53 (0.14) for cariprazine and 0.22 (0.03) for brexpiprazole. Compared with the olanzapine dose equivalents for schizophrenia, those of acute mania were higher for quetiapine (p<0.001, 28.5%) and aripiprazole (p<0.001, 17.0%), but lower for haloperidol (p<0.001, -8.1%) and risperidone (p<0.001, -15.8%).
CONCLUSIONS
Antipsychotic drugs have been considered first-line treatment for acute mania, warranting specific dose equivalence for scientific and clinical purposes.
Topics: Humans; Antipsychotic Agents; Olanzapine; Risperidone; Aripiprazole; Quetiapine Fumarate; Haloperidol; Bipolar Disorder; Mania; Schizophrenia; Randomized Controlled Trials as Topic
PubMed: 36789916
DOI: 10.1136/bmjment-2022-300546 -
Molecular Psychiatry Jul 2023Cross-sectional neuroimaging studies show that bipolar disorder is associated with structural brain abnormalities, predominantly observed in prefrontal and temporal... (Review)
Review
Cross-sectional neuroimaging studies show that bipolar disorder is associated with structural brain abnormalities, predominantly observed in prefrontal and temporal cortex, cingulate gyrus, and subcortical regions. However, longitudinal studies are needed to elucidate whether these abnormalities presage disease onset or are consequences of disease processes, and to identify potential contributing factors. Here, we narratively review and summarize longitudinal structural magnetic resonance imaging studies that relate imaging outcomes to manic episodes. First, we conclude that longitudinal brain imaging studies suggest an association of bipolar disorder with aberrant brain changes, including both deviant decreases and increases in morphometric measures. Second, we conclude that manic episodes have been related to accelerated cortical volume and thickness decreases, with the most consistent findings occurring in prefrontal brain areas. Importantly, evidence also suggests that in contrast to healthy controls, who in general show age-related cortical decline, brain metrics remain stable or increase during euthymic periods in bipolar disorder patients, potentially reflecting structural recovering mechanisms. The findings stress the importance of preventing manic episodes. We further propose a model of prefrontal cortical trajectories in relation to the occurrence of manic episodes. Finally, we discuss potential mechanisms at play, remaining limitations, and future directions.
Topics: Humans; Bipolar Disorder; Mania; Cross-Sectional Studies; Brain; Prefrontal Cortex; Magnetic Resonance Imaging
PubMed: 37147390
DOI: 10.1038/s41380-023-02073-4