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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 Review For Medical and... Oct 2023Bipolar disorder (manic episode) is an essential psychiatric disorder with unknown etiology, in which inflammation is considered to play a role. Klotho and FGF-23 are...
OBJECTIVE
Bipolar disorder (manic episode) is an essential psychiatric disorder with unknown etiology, in which inflammation is considered to play a role. Klotho and FGF-23 are known to be associated with inflammation. Therefore, this study aimed to determine the link between Klotho and FGF-23 levels and bipolar disorder.
PATIENTS AND METHODS
In this study, 42 men with BD and 41 healthy controls were enrolled, followed up, and/or treated at the High-Security Forensic Psychiatry Clinic. Sociodemographic data form, Young Mania Rating Scale, and Hamilton Depression Rating Scale were applied to all participants.
RESULTS
Klotho and FGF-23 levels were significantly increased in patients with BD manic episodes. There was no correlation between Klotho and FGF-23 levels and clinical parameters. For Klotho and FGF-23, cutoff values of 69 and 1,646 yielded 67.4% sensitivity and 72.1% specificity and 81.4% sensitivity and 51.2% specificity, respectively.
CONCLUSIONS
Klotho and FGF-23 may play critical roles in the etiopathology of manic episodes and are potential candidate biomarkers for bipolar disorder. This relationship might contribute to the etiopathogenesis of the disease and determine its treatment. Anti-Klotho and anti-FGF-23 administration may be a future treatment for controlling the course of the disease.
Topics: Male; Humans; Bipolar Disorder; Mania; Inflammation
PubMed: 37869955
DOI: 10.26355/eurrev_202310_34078 -
Revista Brasileira de Psiquiatria (Sao... Jun 2009Literature review of the controlled studies in the last 18 years in emotion recognition deficits in bipolar disorder. (Review)
Review
OBJECTIVE
Literature review of the controlled studies in the last 18 years in emotion recognition deficits in bipolar disorder.
METHOD
A bibliographical research of controlled studies with samples larger than 10 participants from 1990 to June 2008 was completed in Medline, Lilacs, PubMed and ISI. Thirty-two papers were evaluated.
RESULTS
Euthymic bipolar disorder presented impairment in recognizing disgust and fear. Manic BD showed difficult to recognize fearful and sad faces. Pediatric bipolar disorder patients and children at risk presented impairment in their capacity to recognize emotions in adults and children faces. Bipolar disorder patients were more accurate in recognizing facial emotions than schizophrenic patients.
DISCUSSION
Bipolar disorder patients present impaired recognition of disgust, fear and sadness that can be partially attributed to mood-state. In mania, they have difficult to recognize fear and disgust. Bipolar disorder patients were more accurate in recognizing emotions than depressive and schizophrenic patients. Bipolar disorder children present a tendency to misjudge extreme facial expressions as being moderate or mild in intensity.
CONCLUSION
Affective and cognitive deficits in bipolar disorder vary according to the mood states. Follow-up studies re-testing bipolar disorder patients after recovery are needed in order to investigate if these abnormalities reflect a state or trait marker and can be considered an endophenotype. Future studies should aim at standardizing task and designs.
Topics: Bipolar Disorder; Controlled Clinical Trials as Topic; Depressive Disorder; Emotions; Evidence-Based Medicine; Facial Expression; Fear; Humans; Phenotype; Recognition, Psychology; Schizophrenia
PubMed: 19578691
DOI: 10.1590/s1516-44462009000200015 -
Revista Brasileira de Psiquiatria (Sao... 2017Family history and traumatic experiences are factors linked to bipolar disorder. It is known that the lifetime risk of bipolar disorder in relatives of a bipolar proband...
Family history and traumatic experiences are factors linked to bipolar disorder. It is known that the lifetime risk of bipolar disorder in relatives of a bipolar proband are 5-10% for first degree relatives and 40-70% for monozygotic co-twins. It is also known that patients with early childhood trauma present earlier onset of bipolar disorder, increased number of manic episodes, and more suicide attempts. We have recently reported that childhood trauma partly mediates the effect of family history on bipolar disorder diagnosis. In light of these findings from the scientific literature, we reviewed the work of British writer Virginia Woolf, who allegedly suffered from bipolar disorder. Her disorder was strongly related to her family background. Moreover, Virginia Woolf was sexually molested by her half siblings for nine years. Her bipolar disorder symptoms presented a pernicious course, associated with hospitalizations, suicidal behavioral, and functional impairment. The concept of neuroprogression has been used to explain the clinical deterioration that takes places in a subgroup of bipolar disorder patients. The examination of Virgina Woolf's biography and art can provide clinicians with important insights about the course of bipolar disorder.
Topics: Adult Survivors of Child Abuse; Bipolar Disorder; Famous Persons; Female; History, 19th Century; History, 20th Century; Humans; Literature, Modern; Suicide, Attempted
PubMed: 27304258
DOI: 10.1590/1516-4446-2016-1962 -
Translational Psychiatry Apr 2020Psychiatry is constructed around a taxonomy of several hundred diagnoses differentiated by nuances in the timing, co-occurrence, and severity of symptoms. Bipolar... (Review)
Review
Psychiatry is constructed around a taxonomy of several hundred diagnoses differentiated by nuances in the timing, co-occurrence, and severity of symptoms. Bipolar disorder (BD) is notable among these diagnoses for manic, depressive, and psychotic symptoms all being core features. Here, we trace current understanding of the neurobiological origins of BD and related diagnoses. To provide context, we begin by exploring the historical origins of psychiatric taxonomy. We then illustrate how key discoveries in pharmacology and neuroscience gave rise to a generation of neurobiological hypotheses about the origins of these disorders that facilitated therapeutic innovation but failed to explain disease pathogenesis. Lastly, we examine the extent to which genetics has succeeded in filling this void and contributing to the construction of an objective classification of psychiatric disturbance.
Topics: Bipolar Disorder; Humans; Neurobiology; Psychotic Disorders
PubMed: 32327632
DOI: 10.1038/s41398-020-0796-8 -
Acta Psychiatrica Scandinavica Nov 2022Previous research suggests that cognitive performance worsens during manic and depressed states in bipolar disorder (BD). However, studies have often relied upon...
OBJECTIVES
Previous research suggests that cognitive performance worsens during manic and depressed states in bipolar disorder (BD). However, studies have often relied upon between-subject, cross-sectional analyses and smaller sample sizes. The current study examined the relationship between mood symptoms and cognition in a within-subject, longitudinal study with a large sample.
METHODS
Seven hundred and seventy-three individuals with BD completed a neuropsychological battery and mood assessments at baseline and 1-year follow-up. The battery captured eight domains of cognition: fine motor dexterity, visual memory, auditory memory, emotion processing, and four aspects of executive functioning: verbal fluency and processing speed; conceptual reasoning and set shifting; processing speed with influence resolution; and inhibitory control. Structural equation modeling was conducted to examine the cross-sectional and longitudinal relationships between depressive symptoms, manic symptoms, and cognitive performance. Age and education were included as covariates. Eight models were run with the respective cognitive domains.
RESULTS
Baseline mood positively predicted 1-year mood, and baseline cognition positively predicted 1-year cognition. Mood and cognition were generally not related for the eight cognitive domains. Baseline mania was predictive in one of eight baseline domains (conceptual reasoning and set shifting); baseline cognition predicted 1-year symptoms (inhibitory control-depression symptoms, visual memory-manic symptoms).
CONCLUSIONS
In a large community sample of patients with bipolar spectrum disorder, cognitive performance appears to be largely unrelated to depressive and manic symptoms, suggesting that cognitive dysfunction is stable in BD and is not dependent on mood state in BD. Future work could examine how treatment affects relationship between cognition and mood.
SIGNIFICANT OUTCOMES
Cognitive dysfunction appears to be largely independent of mood symptoms in bipolar disorder.
LIMITATIONS
The sample was generally highly educated (M = 15.22), the majority of the subsample with elevated manic symptoms generally presented with concurrent depressive elevated symptoms, and the study did not stratify recruitment based on mood state.
Topics: Bipolar Disorder; Cognition; Cognition Disorders; Cross-Sectional Studies; Humans; Longitudinal Studies; Neuropsychological Tests
PubMed: 35426440
DOI: 10.1111/acps.13436 -
Journal of Psychiatric Research Feb 2022While the favorable effect of adjuvant clonidine in the treatment of acute mania has been observed already about 40 years ago, this line of treatment has not been... (Randomized Controlled Trial)
Randomized Controlled Trial
Influence of adjuvant clonidine on mania, sleep disturbances and cognitive performance - Results from a double-blind and placebo-controlled randomized study in individuals with bipolar I disorder during their manic phase.
BACKGROUND
While the favorable effect of adjuvant clonidine in the treatment of acute mania has been observed already about 40 years ago, this line of treatment has not been further investigated. Here, we resumed this topic, and we tested the effect of adjuvant clonidine, an antihypertensive stimulating the alpha- central adrenergic receptor, on symptoms of mania, cognitive performance, and subjective sleep. To this end, we performed a randomized, double-blind and placebo-controlled clinical trial among inpatients with bipolar disorder I during their acute phase of mania.
METHODS
A total of 70 inpatients (mean age: 37.40 years; 15.7% females) with diagnosed bipolar disorder I and during their acute manic phase were randomly assigned either to the adjuvant clonidine (0.2 mg/d to a maximum of 0.6 mg/d) or to the placebo condition. Standard medication was lithium at therapeutic dosages. At baseline, participants completed a series of self-rating questionnaires covering sociodemographic information and subjective sleep. Subjective sleep was re-assessed 24 days later at the end of the study. Experts rated participants' acute state of mania with the Young Mania Rating Scale at baseline and at day 12 and day 24. Participants' cognitive performance was assessed at baseline and at day 24 at the end of the study.
RESULTS
Over time, mania scores significantly decreased (large effect size), but more so in the clonidine condition, compared to the placebo condition (medium effect size). Likewise, over time, subjective sleep improved (large effect size), but more so in the clonidine, compared to the placebo condition (medium effect size). Over time, cognitive performance improved (medium effect size), irrespective from the study condition.
CONCLUSIONS
Compared to placebo, adjuvant clonidine to lithium improved symptoms of mania, as rated by experts', and subjective sleep quality. Adjuvant clonidine had no further favorable (or detrimental) impact on cognitive performance.
Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Clonidine; Cognition; Double-Blind Method; Female; Humans; Male; Mania; Psychiatric Status Rating Scales; Sleep; Treatment Outcome
PubMed: 34990968
DOI: 10.1016/j.jpsychires.2021.12.035 -
Neurosciences (Riyadh, Saudi Arabia) Jan 2019To examine the association between clinical and treatment characteristics and antidepressants (AD)-induced manic switch in bipolar disorder (BD).
OBJECTIVE
To examine the association between clinical and treatment characteristics and antidepressants (AD)-induced manic switch in bipolar disorder (BD).
METHODS
Total of 238 euthymic BD patients, who had been followed-up for at least 6 months at the outpatient clinic of Haseki Training and Research Hospital in istanbul, Turkey, were enrolled in this cross-sectional study in 2016. Semi-structured data form, the mood chart, and the mirror-designated assessment were applied to all subjects. The files of the patients were retrospectively reviewed and the patients using ADs were compared as AD-monotherapy (AD-m) and AD-combination (AD-c) groups, then divided into 2 subgroups according to the presence/absence of manic switch under AD treatment.
RESULTS
Fifty eight (47.15%) patients out of 123 who received ADs at least once had experienced a manic switch under AD treatment. The rate of manic switch in AD-m patients was significantly higher than the AD-c group. Independent from being monotherapy or combined treatment, AD use longer than 12 months was negatively associated with the occurrence of manic switch.
CONCLUSION
Our study suggests that the risk of manic switch is especially prominent in the first months of AD use. Antidepressants use in combining it with a mood stabilizers (MS) may not be adequate in preventing switches in shorter terms. However, in longer term uses addition of MS to ADs may decrease the risk of switches.
Topics: Adult; Antidepressive Agents; Bipolar Disorder; Drug Combinations; Female; Humans; Male; Middle Aged
PubMed: 30842399
DOI: 10.17712/nsj.2019.1.20180008 -
PloS One 2013Bipolar disorder is characterized by severe mood symptoms including major depressive and manic episodes. During manic episodes, many patients show cognitive dysfunction....
INTRODUCTION
Bipolar disorder is characterized by severe mood symptoms including major depressive and manic episodes. During manic episodes, many patients show cognitive dysfunction. Dopamine and glutamate are important for cognitive processing, thus the COMT and DAOA genes that modulate the expression of these neurotransmitters are of interest for studies of cognitive function.
METHODOLOGY
Focusing on the most severe episode of mania, a factor was found with the combined symptoms of talkativeness, distractibility, and thought disorder, considered a cognitive manic symptoms (CMS) factor. 488 patients were genotyped, out of which 373 (76%) had talkativeness, 269 (55%) distractibility, and 372 (76%) thought disorder. 215 (44%) patients were positive for all three symptoms, thus showing CMS (Table 1). As population controls, 1,044 anonymous blood donors (ABD) were used. Case-case and case-control design models were used to investigate genetic associations between cognitive manic symptoms in bipolar 1 disorder and SNPs in the COMT and DAOA genes. [Table: see text].
RESULTS
The finding of this study was that cognitive manic symptoms in patients with bipolar 1 disorder was associated with genetic variants in the DAOA and COMT genes. Nominal association for DAOA SNPs and COMT SNPs to cognitive symptoms factor in bipolar 1 disorder was found in both allelic (Table 2) and haplotypic (Table 3) analyses. Genotypic association analyses also supported our findings. However, only one association, when CMS patients were compared to ABD controls, survived correction for multiple testing by max (T) permutation. Data also suggested interaction between SNPs rs2391191 in DAOA and rs5993883 in COMT in the case-control model. [Table: see text] [Table: see text].
CONCLUSION
Identifying genes associated with cognitive functioning has clinical implications for assessment of prognosis and progression. Our finding are consistent with other studies showing genetic associations between the COMT and DAOA genes and impaired cognition both in psychiatric disorders and in the general population.
Topics: Alleles; Bipolar Disorder; Carrier Proteins; Case-Control Studies; Catechol O-Methyltransferase; Female; Gene Frequency; Genetic Association Studies; Genotype; Humans; Intracellular Signaling Peptides and Proteins; Linkage Disequilibrium; Male; Odds Ratio; Polymorphism, Single Nucleotide
PubMed: 23861766
DOI: 10.1371/journal.pone.0067450 -
International Journal of Molecular... Feb 2022Bipolar disorder (BD) is a severe psychiatric illness with a poor prognosis and problematic, suboptimal, treatments. Treatments, borne of an understanding of the... (Review)
Review
Bipolar disorder (BD) is a severe psychiatric illness with a poor prognosis and problematic, suboptimal, treatments. Treatments, borne of an understanding of the pathoetiologic mechanisms, need to be developed in order to improve outcomes. Dysregulation of cationic homeostasis is the most reproducible aspect of BD pathophysiology. Correction of ionic balance is the universal mechanism of action of all mood stabilizing medications. Endogenous sodium pump modulators (collectively known as endogenous cardiac steroids, ECS) are steroids which are synthesized in and released from the adrenal gland and brain. These compounds, by activating or inhibiting Na, K-ATPase activity and activating intracellular signaling cascades, have numerous effects on cell survival, vascular tone homeostasis, inflammation, and neuronal activity. For the past twenty years we have addressed the hypothesis that the Na, K-ATPase-ECS system may be involved in the etiology of BD. This is a focused review that presents a comprehensive model pertaining to the role of ECS in the etiology of BD. We propose that alterations in ECS metabolism in the brain cause numerous biochemical changes that underlie brain dysfunction and mood symptoms. This is based on both animal models and translational human results. There are data that demonstrate that excess ECS induce abnormal mood and activity in animals, while a specific removal of ECS with antibodies normalizes mood. There are also data indicating that circulating levels of ECS are lower in manic individuals, and that patients with BD are unable to upregulate synthesis of ECS under conditions that increase their elaboration in non-psychiatric controls. There is strong evidence for the involvement of ion dysregulation and ECS function in bipolar illness. Additional research is required to fully characterize these abnormalities and define future clinical directions.
Topics: Animals; Bipolar Disorder; Brain; Down-Regulation; Humans; Ion Pumps; Signal Transduction; Steroids
PubMed: 35163766
DOI: 10.3390/ijms23031846