Association of childhood trauma, social support, cognition, and suicidality in females with bipolar disorder.

BACKGROUND: Bipolar disorder (BD) is a severe mental disorder with heavy disease burden. Females with BD are special populations who suffer a lot from childhood trauma, social support, cognitive deficits, and suicidality. In this study, the relationship among childhood trauma, social support, and clinical symptoms of BD was investigated and the risk factors for suicidality were explored in female patients with BD. METHODS: This study included 57 drug-naive female BD patients, 64 female BD patients with long-term medication, and 50 age-matched female healthy controls. Childhood trauma, social support, clinical symptoms, cognition, and suicidality (suicide ideation, suicide plan, suicide attempt, suicide frequency) were measured with scales. RESULTS: Compared with healthy controls, females with BD showed higher levels of childhood trauma and suicidality, and lower levels of social support and cognitive deficits. In the drug-naïve BD group, social support mediated the relationship between childhood trauma and insomnia symptoms (indirect effect: ab = 0.025). In the BD with long-term medication group, mania symptom was associated with suicide plan (OR = 1.127, p = 0.030), childhood trauma was associated with suicide attempt (OR = 1.088, p = 0.018), and years of education (OR = 0.773, p = 0.028), childhood trauma (OR = 1.059, p = 0.009), and delayed memory (OR= 1.091, p= 0.016) was associated with suicide frequency (OR = 1.091, p = 0.016). CONCLUSIONS: This study provides initial evidence that social support partially explains the relationship between childhood trauma and clinical symptoms in females with BD. Additionally, mania symptoms, childhood trauma, and delayed memory were risk factors for suicidality. Interventions providing social support and improving cognitive function may be beneficial for females with BD who are exposed to childhood trauma and with high suicide risk.

Deficits in sustained attention in adolescents with bipolar disorder during their first manic episode.

OBJECTIVES: Evaluate differences in sustained attention (SAT) and associated neurofunctional profiles between bipolar disorder type I (BD), attention-deficit/hyperactivity disorder (ADHD), and healthy comparison (HC) youth. METHODS: Adolescent participants, aged 12-17 years, with BD (n = 30) and ADHD (n = 28) and HC adolescents (n = 26) underwent structural and functional magnetic resonance imaging (fMRI) while completing a modified Continuous Performance Task-Identical Pairs task. Attentional load was modifying in this task using three levels of image distortion (0 %, 25 % and 50 % image distortion). Task related fMRI activation and performance measures: perceptual sensitivity index (PSI); response bias (RB) and response time (RT); were calculated and compared between groups. RESULTS: BD participants displayed lower perceptual sensitivity index (0 % p = 0.012; 25 % p = 0.015; 50 % p = 0.036) and higher values of response bias across levels of distortion (0 % p = 0.002, 25 % p = 0.001, and 50 % p = 0.008) as compared to HC. No statistically significant differences were observed for PSI and RB between BD and ADHD groups. No difference in RT were detected. Between-group and within-group differences in task related fMRI measures were detected in several clusters. In a region of interest (ROI) analysis of these clusters comparing BD and ADHD confirmed differences between these two groups. CONCLUSIONS: Compared with HC, BD participants displayed SAT deficits. Increased attentional load revealed that BD participants had lower activation in brain regions associated with performance and integration of neural processes in SAT. ROI analysis between BD and ADHD participants shows that the differences were likely not attributable to ADHD comorbidity, suggesting SAT deficits were distinct to the BD group.

Hormonal and inflammatory signatures of different mood episodes in bipolar disorder: a large-scale clinical study.

BACKGROUND: Bipolar disorder (BD) is characterized by intensive mood fluctuations. While hormones imbalance plays important role in the mood swings, it is unknown whether peripheral hormones profiles could differentiate the manic and depressive mood episodes in BD. In this study, we investigated the changes of various hormones and inflammatory markers across distinct mood episodes of BD in a large clinical study to provide mood episode-specific peripheral biomarkers for BD. METHODS: A total of 8332 BD patients (n = 2679 depressive episode; n = 5653 manic episode) were included. All patients were in acute state of mood episodes and need hospitalization. A panel of blood tests were performed for levels of sex hormones (serum levels of testosterone, estradiol, and progesterone), stress hormones (adrenocorticotropic hormone and cortisol), and an inflammation marker (C-reactive protein, CRP). A receiver operating characteristic (ROC) curve was used to analyze the discriminatory potential of the biomarkers for mood episodes. RESULTS: In overall comparison between mood episodes, the BD patients expressed higher levels of testosterone, estradiol, progesterone, and CRP (P < 0.001) and lower adrenocorticotropic hormone (ACTH) level (P < 0.001) during manic episode. The episode-specific changes of testosterone, ACTH, and CRP levels remained between the two groups (P < 0.001) after correction for the confounding factors including age, sex, BMI, occupation, marital status, tobacco use, alcohol consumption, psychotic symptoms, and age at onset. Furthermore, we found a sex- and age-specific impact of combined biomarkers in mood episodes in male BD patients aged ≥ 45 years (AUC = 0.70, 95% CI, 0.634-0.747), not in females. CONCLUSIONS: While both hormone and inflammatory change is independently associated with mood episodes, we found that the combination of sex hormones, stress hormones and CRP could be more effective to differentiate the manic and depressive episode. The biological signatures of mood episodes in BD patients may be sex- and age-specific. Our findings not only provide mood episode-related biological markers, but also better support for targeted intervention in BD treatments.

Acute Mania in a Patient With Primary Adrenal Insufficiency Due to Autoimmune Adrenalitis: A Case Report.

We describe a rare case of acute mania in the setting of autoimmune adrenalitis. A 41-year-old male with no previous psychiatric diagnoses presented with impulsivity, grandiosity, delusions of telepathy, and hyperreligiosity following a previous hospitalization for an acute adrenal crisis and 2 subsequent days of low-dose corticosteroid treatment. Workups for encephalopathy and lupus cerebritis were negative, raising concern that this presentation might represent steroid-induced psychosis. However, discontinuation of corticosteroids for 5 days did not resolve the patient's manic episode, suggesting that his clinical presentation was more likely new onset of a primary mood disorder or a psychiatric manifestation of adrenal insufficiency itself. The decision was made to restart corticosteroid treatment for the patient's primary adrenal insufficiency (formerly known as Addison disease), coupled with administration of both risperidone and valproate for mania and psychosis. Over the following 2 weeks, the patient's manic symptoms resolved, and he was discharged home. His final diagnosis was acute mania secondary to autoimmune adrenalitis. Although acute mania in adrenal insufficiency is quite rare, clinicians should be aware of the range of psychiatric manifestations associated with Addison disease so that they can pursue the optimal course of both medical and psychiatric treatment for these patients.

Exploring Digital Biomarkers of Illness Activity in Mood Episodes: Hypotheses Generating and Model Development Study.

BACKGROUND: Depressive and manic episodes within bipolar disorder (BD) and major depressive disorder (MDD) involve altered mood, sleep, and activity, alongside physiological alterations wearables can capture. OBJECTIVE: Firstly, we explored whether physiological wearable data could predict (aim 1) the severity of an acute affective episode at the intra-individual level and (aim 2) the polarity of an acute affective episode and euthymia among different individuals. Secondarily, we explored which physiological data were related to prior predictions, generalization across patients, and associations between affective symptoms and physiological data. METHODS: We conducted a prospective exploratory observational study including patients with BD and MDD on acute affective episodes (manic, depressed, and mixed) whose physiological data were recorded using a research-grade wearable (Empatica E4) across 3 consecutive time points (acute, response, and remission of episode). Euthymic patients and healthy controls were recorded during a single session (approximately 48 h). Manic and depressive symptoms were assessed using standardized psychometric scales. Physiological wearable data included the following channels: acceleration (ACC), skin temperature, blood volume pulse, heart rate (HR), and electrodermal activity (EDA). Invalid physiological data were removed using a rule-based filter, and channels were time aligned at 1-second time units and segmented at window lengths of 32 seconds, as best-performing parameters. We developed deep learning predictive models, assessed the channels' individual contribution using permutation feature importance analysis, and computed physiological data to psychometric scales' items normalized mutual information (NMI). We present a novel, fully automated method for the preprocessing and analysis of physiological data from a research-grade wearable device, including a viable supervised learning pipeline for time-series analyses. RESULTS: Overall, 35 sessions (1512 hours) from 12 patients (manic, depressed, mixed, and euthymic) and 7 healthy controls (mean age 39.7, SD 12.6 years; 6/19, 32% female) were analyzed. The severity of mood episodes was predicted with moderate (62%-85%) accuracies (aim 1), and their polarity with moderate (70%) accuracy (aim 2). The most relevant features for the former tasks were ACC, EDA, and HR. There was a fair agreement in feature importance across classification tasks (Kendall W=0.383). Generalization of the former models on unseen patients was of overall low accuracy, except for the intra-individual models. ACC was associated with "increased motor activity" (NMI>0.55), "insomnia" (NMI=0.6), and "motor inhibition" (NMI=0.75). EDA was associated with "aggressive behavior" (NMI=1.0) and "psychic anxiety" (NMI=0.52). CONCLUSIONS: Physiological data from wearables show potential to identify mood episodes and specific symptoms of mania and depression quantitatively, both in BD and MDD. Motor activity and stress-related physiological data (EDA and HR) stand out as potential digital biomarkers for predicting mania and depression, respectively. These findings represent a promising pathway toward personalized psychiatry, in which physiological wearable data could allow the early identification and intervention of mood episodes.

Prevalence of ADHD in a Sample of Heroin Addicts Receiving Agonist Treatment-Study Conducted in a Public Addiction Service.

Attention-deficit/hyperactivity disorder (ADHD) is a childhood neurodevelopmental disorder that can persist into adulthood. The co-occurrence of ADHD and substance use disorders is very frequent and has received considerable attention in recent clinical/scientific investigations. However, few studies have investigated the prevalence of ADHD in heroin addicts. This study aimed to investigate the prevalence of attention-deficit/hyperactivity disorder (ADHD) in a sample of heroin addicts treated with opioid agonists and to report this clinical experience in a public service for addiction. Outpatients over 18 years old and being treated with opioid agonists for heroin addiction were enrolled. Each patient took part in a psychiatric examination and completed an ASRS (Adult ADHD Self-Report Scale) self-assessment. Subjects with positive results were called in for another psychiatric visit, and the Brown ADD scale was used as a second-level test for ADHD; furthermore, the Mini International Neuropsychiatric Interview (MINI) and Hypomania/Mania Checklist (HCL-32) were used for differential diagnoses and to assess comorbidities. In total, 111 patients were enrolled. All were followed up by the psychiatrist, who is also the author of this report and the person who formulated the diagnoses. The prevalence of ADHD in this sample was 18%. Among the 20 patients diagnosed with ADHD, 5 (25%) were female and 15 (75%) were male. The most frequent psychiatric comorbidity was major depression, found in 11 patients (55%), of which 4 presented with hypomania (bipolar disorder). In this sample, making diagnoses was very difficult. Frequently, multiple comorbidities further complicated these cases. In conclusion, the results of this study are consistent with the literature: There seems to be a significant prevalence of ADHD even among heroin addicts, and often, the diagnosis is difficult to make. We also do not know the exact effect of opioid agonist therapy on ADHD symptoms. Hypotheses have been put forward, but studies are needed.

Associations between emotional and non-emotional cognition and subsequent mood episodes in recently diagnosed patients with bipolar disorder: A 16-month follow-up study.

BACKGROUND: Bipolar disorder (BD) is associated with impairments in both emotional and non-emotional cognition. Recently, cognitive impairments have attracted increasing research interest as markers of prognosis and possible treatment targets in patients with BD. However, there is a paucity of studies investigating cognitive predictors of prognosis in BD. METHODS: We assessed 148 recently diagnosed, symptomatically stable patients with BD with a battery of emotional and non-emotional cognitive tests and followed them up over 16 months as part of an ongoing cohort study. Multiple linear regression analyses were conducted to examine the associations between cognitive performance at baseline and the recurrence and duration of (hypo)manic and depressive episodes, respectively, with adjustment for age, sex, subsyndromal symptoms and time between assessments. RESULTS: Poorer recognition of negative facial expressions and more negative emotions in neutral daily life scenarios were associated with greater frequency (ps ≤ .04) and longer duration (ps ≤ .03) of subsequent (hypo)manic episodes over the 16-month follow-up period. In addition, poorer global cognition, attention and psychomotor speed, and verbal fluency were associated with more (hypo)manic episodes (ps ≤ .04). Finally, more difficulty down-regulating emotion in negative social scenarios was associated with depressive relapse (p = .007). It was a limitation that patients had a delayed diagnosis of seven years from their first mood episode despite being recently diagnosed. CONCLUSION: Trait-related cognitive impairments influence the early course in recently diagnosed patients with BD, particularly (hypo)manic relapse. Early prophylactic strategies targeting cognitive impairments may increase resilience and the course of illness in recently diagnosed patients with BD.

Antenatal screening of depressive and manic symptoms in south Brazilian childbearing women: A transversal study in advance of the pandemic scenario.

BACKGROUND: The diagnosis of mood disorders (MD) during pregnancy is challenging and may bring negative consequences to the maternal-fetal binomial. The long waitlist for specialized psychiatric evaluation in Brazil contributes to the treatment omission. Almost 20.0% of women treated with antidepressants have a positive screening for bipolar disorder. Therefore, it has been recommended the investigation of depressive and bipolar disorder during prenatal care. Unfortunately, the screening for mood disorders is not a reality in Brazil and many childbearing women remain undiagnosed. The objective of this study is to observe the frequency of MD and the effectiveness of screening scales for routine use by health professionals during prenatal care in high-risk pregnancies. METHODOLOGY/PRINCIPAL FINDINGS: This cross-sectional study included 61 childbearing women in their second trimester who were interviewed using the Edinburgh Postnatal Depression Scale (EPDS) and the Mood Disorder Questionnaire (MDQ). The cut-off point was EPDS ≥ 13 and MDQ ≥ 7 and the SCID-5 was the gold standard diagnosis. MD were diagnosed in 24.6% of the high-risk pregnancies. EDPS was positive in 19.7% and the frequency of major depression was 8.2%. 16.4% of the childbearing women were diagnosed with bipolar disorder, while MDQ was positive in 36.1%. 11.5% of the women had EPDS and MDQ positive. EPDS sensitivity was 80.0% and specificity 92.1%, whereas MDQ presented a sensitivity of 70.0% and specificity of 70.6%. CONCLUSION/SIGNIFICANCE: There is a high prevalence of MD in high-risk pregnancies. The routine use of EPDS simultaneously to MDQ during antenatal care is effective and plays an important role in early diagnosis, counselling, and promotion of perinatal mental health.

Lurasidone-Induced Manic Switch in an Adolescent with Bipolar I Disorder: a Case Report.

Lurasidone is used for treatment of bipolar depression in adults and adolescents. Lurasidone-associated manic switch has been reported in adults but not yet in adolescents. We report a case of lurasidone-induced manic switch in a male adolescent treated for bipolar I depression. Five days after adding lurasidone to his regimen (sodium valproate and olanzapine), our patient became manic with psychotic features. After discontinuation of lurasidone, he was stabilised with electroconvulsive therapy, and the medication was switched to a lithium-quetiapine combination. This case highlights the potential risk of lurasidone-induced manic switch in adolescents with bipolar depression.

Switch to Hypomania After Discontinuation of Tamoxifen: A Case Report.

Tamoxifen is a synthetic, nonsteroidal antiestrogen widely used in the treatment of hormone-sensitive breast cancer that has also been shown to inhibit the enzyme protein kinase C (PKC). Upregulation of PKC is associated with disruption of prefrontal cortical regulation of thinking and behavior, which can lead to mania-like symptoms in animal models. Lithium and valproate, 2 mood stabilizers that are widely used in the treatment of bipolar disorder, have also been shown to inhibit PKC. We describe the case of a 48-year-old woman who entered a hypomanic state after discontinuation of tamoxifen while remaining on unopposed venlafaxine prescribed for depression. This case highlights the risk of misdiagnosing unipolar depression in breast cancer patients with undiagnosed bipolar disorder who are being treated with tamoxifen and subsequently started on antidepressants. The use of antidepressants in this population should be carefully monitored to avoid the development of manic, hypomanic, or mixed symptoms in patients with underlying bipolar disorder once tamoxifen is discontinued.

A New Onset of Mania in a 49-Year-Old Man: An Interesting Case of Wilson Disease.

Wilson disease is a rare copper metabolism disorder that generally occurs in individuals between 5 and 35 years of age. Common clinical manifestations are hepatic, neurological, and psychiatric symptoms. Roughly, 4% of all cases occur in patients over 40 years of age and, among these patients, the presenting symptoms are generally neuropsychiatric, which often leads to misdiagnosis as a primary psychiatric disorder and a delay in correct diagnosis. This report presents the case of a 49-year-old man with no formal psychiatric history who presented with a new onset of mania. We outline the distinctive characteristics that appeared inconsistent with a primary psychiatric disorder and pointed toward secondary mania. Despite low serum ceruloplasmin, the absence of brain abnormalities more typical of Wilson disease on magnetic resonance imaging led a neurology consultant to advise that the diagnosis was likely primarily psychiatric. Due to atypical components of the patient's presentation, such as his late age of onset for bipolar disorder and acute cognitive decline, the psychiatric team advocated for further diagnostic workup. The subsequent evaluation confirmed Wilson disease based on specific ophthalmological and hepatic abnormalities and further copper studies. In addition, once diagnosed, the management of Wilson disease involves distinct clinical considerations given patients' presumed vulnerability to neurological side effects. This case illustrates the role psychiatric providers play in advocating for diagnostic workup in patients with atypical presentations of primary psychiatric disorders and the distinct diagnostic and treatment considerations associated with Wilson disease.

Foreign accent syndrome in a patient with posturemic encepalopathy.

Foreign accent syndrome (FAS) is a rare, poorly understood speech disorder. It is characterized by the patient speaking their native language in a different accent foreign to both the speaker and the listener. A majority of previously reported cases have been described in patients with diagnosed organic brain damage and a handful of other psychiatric disorders. FAS was not the result of language experience in our index patient, and there is no history of the patient ever visiting the United States of America. This case is presented because it is the first-ever seen case in the environment.

Résumé Le syndrome de l'accent étranger (SAF) est un trouble de la parole rare et mal compris. Elle se caractérise par le fait que le patient parle sa langue maternelle dans un accent différent étranger à la fois au locuteur et à l'auditeur. La majorité des cas précédemment rapportés ont été décrits chez des patients diagnostiqué des lésions cérébrales organiques et une poignée d'autres troubles psychiatriques. Le SAF n'était pas le résultat d'une expérience linguistique dans notre index patient, et il n'y a pas d'antécédents de visite du patient aux États-Unis d'Amérique. Ce cas est présenté parce que c'est le premier jamais vu cas dans l'environnement.

Severe Hypothyroidism Manifested as Acute Mania With Psychotic Features: A Case Report and Review of the Literature.

Hypothyroidism is associated with a wide array of medical, neurological, and psychiatric symptoms. Severe hypothyroidism may present as myxedema coma, a medical emergency. In addition, patients may present with myxedema psychosis, a psychiatric emergency manifested as hyperactive encephalopathy, hallucinations, delusions, and suicidal ideation. In rare instances, patients may present with symptoms of mania with psychosis. We present the case of a 26-year-old woman with no known psychiatric history who presented with gradual onset of altered mental status, distractibility, decreased need for sleep, pressured speech, and religious and paranoid delusions. Her medical history was significant for a surgically absent thyroid gland and nonadherence to thyroid hormone. The patient was found to have a severely elevated level of thyroid-stimulating hormone, low level of triiodothyronine, and undetectable thyroxine. Thyroid ultrasound demonstrated a surgically absent thyroid gland. The patient's metabolic panel and random serum cortisol level were normal. Rapid plasma reagin was nonreactive, and toxin screening was negative. It was concluded that severe hypothyroidism was the cause of the patient's mania with psychotic features, given her thyroid hormone levels and lack of history of a psychiatric or substance use disorder. Thyroid hormone monitoring and treatment of hypothyroidism is necessary in all patients who have undergone surgical excision of the thyroid gland. All patients presenting with a first episode mania should be screened for thyroid dysfunction. The preferred treatment includes an atypical antipsychotic and thyroid replacement therapy. Rapid resolution of symptoms can occur with combined levothyroxine and liothyronine. Correction of hypothyroidism improves response to antipsychotics.

A Case of Arachnoid Cyst Presenting with Cognitive Impairment and Hypomania Symptoms. / Bilissel Bozukluk ve Hipomani Belirtileriyle Basvuran Bir Araknoid Kist Olgusu.

Arachnoid cysts are benign congenital malformations of the arachnoid which account for approximately 1.4% of the intracranial lesions. Although it is usually asymptomatic, it may be accompanied by headache, hydrocephalus and seizure. Psychiatric disorders associated with arachnoid cysts are rare. In this article, we present a giant arachnoid cyst with hypomania symptoms and marked cognitive impairment. A 44-year-old female patient was admitted to our outpatient clinic with a 4-year history of headache, nervousness and attention problems. Magnetic resonance imaging revealed a giant arachnoid cyst with a size of 5.5x10.5x12.5 cm was found in the left hemisphere of the patient. Considering the patient's irritability, increase in the amount of speech, flight of ideas, sleep disturbance and attention disorders, the diagnosis of hypomania was made. The neuropsychological tests showed that the speed of information processing, mental flexibility and attention functions decreased, and executive functions were impaired. The patient was consulted to the neurosurgery department. But no surgical treatment was offered. Drug therapy for hypomanic symptoms and cognitive impairment was planned, but could not be started since the patient did not attend to the follow-up exams. Albeit the lack of followup constitutes a limitation for our report, we believe that the size of the cyst, significant impairment of cognitive functions and the presence of hypomania symptoms might contribute significantly to the literature. Other cases with arachnoid cyst displaying cognitive impairment were summarized in our article.

Efficacy of melatonin as an adjunct in the treatment of acute mania: a double-blind and placebo-controlled trial.

This is a double-blind, placebo-controlled, parallel-grouped clinical trial, which was designed to investigate the potential effects of melatonin add-on treatment with lithium and risperidone on acute manic episodes in patients with bipolar disorder (BD). A total of 54 patients were included and randomly assigned into two groups of melatonin and placebo. The trial group received 3 mg/day risperidone, 900 mg/day lithium, and 6 mg/day melatonin. The placebo group received the same dose of risperidone and lithium plus placebo. The participants were evaluated at four sessions, consisting of baseline, weeks 1, 4, and 6. The manic symptoms and overall clinical improvement of the patients were assessed using the Young Mania Rating Scale (YMRS) and Clinical Global Impressions-Improvement (CGI-I), respectively. Two trial groups were matched based on all baseline characteristics. The patients in two trial groups had comparable serum lithium levels at weeks 1, 4, and 6. Our results from the general linear model repeated measures analysis showed a significant effect for time × treatment interaction on YMRS scores (P = 0.021 and F-value = 3.7). Furthermore, outcomes of the CGI-I rating scale demonstrated that patients in the melatonin group had better clinical improvements compared to the placebo group (P = 0.018). Our results provided preliminary evidence supporting melatonin as an effective adjunctive treatment leading to significant improvements in manic symptoms and overall clinical status in acute episodes of mania.

O intenso e vazio viver maníaco-melancólico / The intense and empty existence of the manic-melancholic

Introdução: A experiência maníaco-melancólica é marcada pelo sofrimento, restrição e perda da liberdade em seu modo-de-ser-no-mundo. É comum atitudes de estranhamento, afastamento não só da pessoa que vive essa experiência, como dos entes ao seu redor. Objetivos: Buscar uma aproximação entre a Mania e a Melancolia, considerando algumas similaridades na vivência dos existenciais como a espacialidade, a temporalidade, a corporeidade e a afinação. Métodos: Realizou-se uma revisão bibliográfica acerca da vivência maníaco-melancólica, pautada nos pressupostos do referencial Fenomenológico-Existencial. Resultados: Percebemos em ambas experiências um não desdobramento do tempo, uma não realização das possibilidades futuras, um não relacionamento com as coisas do mundo e uma perda de projeção da corporeidade no mundo.Conclusão: A Mania e a Melancolia são compreendidas não como uma doença, mas como um modo de ser no mundo em que a liberdade de escolhas de vir a ser encontra-se limitada.

Introduction: The manic-melancholic experience is marked by suffering, loss of freedom and constraint in their way-of-being in the world. It is common attitudes of estrangement, isolation not only the person living that experience, as the beings around him. Objectives: To find a rapprochement between mania and melancholy, considering some similarities in the experience of existential as spatiality, temporality, corporeality and tuning. Methods: We conducted a literature review about the manic-melancholic experience, based on the assumptions of the phenomenological approach: Existential. Results: We noticed in both experiments a non-split time, not a realization of future possibilities, not a relationship with things in the world and a loss of projection of embodiment in mundo.Conclusão: mania and melancholia are understood not as a disease, but as a way of being in the world where freedom of choice of being is limited.