Mania Research Articles

Valproic acid-induced hyperammonemic encephalopathy: a clinical case

IntroductionValproic acid is a psychotropic drug used for several years, due to its properties as a mood stabilizer, being considered as first-line treatment for bipolar disorder. In addition to its teratogenic potential, which prevents its recommendation for the treatment of bipolar disorder in women of childbearing age, valproic acid is associated with some side effects, such as gastrointestinal symptoms, alopecia, weight gain, tremor or hepatotoxicity. Hyperammonemia is a side effect that is little described, but relatively frequent, and may progress to variable encephalopathy.ObjectivesThe authors describe a clinical case of a 48-year-old female patient, hospitalized due to a manic episode, who was prescribed valproic acid, in association with lorazepam and olanzapine.MethodsAfter three days on a dose of 1000mg of valproic acid, the patient began an acute condition of confusion, psychomotor retardation, temporal-spatial disorientation and ataxia. Infection, electrolyte disturbance and acute cerebral event were excluded. Noteworthy only hyperammonemia. Valproic acid was withdrawn and replaced by lithium, with the patient recovering from the confusional state two days later.ResultsHyperamonemic encephalopathy secondary to valproic acid was concluded. The mechanisms of valproic acid-linked hyperammonemia are not clear, although it appears to be independent of hepatotoxicity. The most studied hypotheses are related to glutamine reabsorption and serum levels carnitine in patients medicated with valproic acid.ConclusionsIt is essential that there is a high level of suspicion in clinicians for this secondary effect of valproic acid, in order to adequately treat the patient who presents with acute confusional conditions, not explained by other complications.DisclosureNo significant relationships.

Long-term brain changes in bipolar disorder

IntroductionThe term “neuroprogression” imply that bipolar disorder (BD) progressively worsens for some patients and accompanying neuroanatomical changes. BD has indeed been associated with cortical and subcortical brain abnormalities. But cross-sectional studies cannot determine whether the observed brain alterations reflect static premorbid traits or whether they result from progressive changes during the course of illness.ObjectivesThe aims of this series of studies were to determine if progressive brain changes occur in bipolar disorder, and if so, what the drivers of these changes are.MethodsWe addressed these questions in the St. Göran cohort – a longitudinal study where patients and controls undergo structural magnetic resonance imaging (MRI) scans at baseline and after 7 years. We have also conducted a longitudinal multicenter study within the ENIGMA consortium including 307 patients and 925 healthy controls scanned at two time points.ResultsWe addressed these questions in the St. Göran cohort – a longitudinal study where patients and controls undergo structural magnetic resonance imaging (MRI) scans at baseline and after 7 years. We have also conducted a longitudinal multicenter study within the ENIGMA consortium including 307 patients and 925 healthy controls scanned at two time points.ConclusionsBD is associated with some (accelerated ventricular enlargement) but not global progressive brain changes (change in cortical structures do not differ from controls). Occurrence of manic episodes is, however, associated with accelerated cortical thinning over time. These results highlight the importance of preventing the potentially toxic effects of manic episodes and might explain why some patients experience worsening cognitive function.DisclosureML has received lecture honoraria (unrelated to this topic) from Lundbeck pharmaceuticals.

Chronic, Unipolar, Treatment-Resistant Mania: A Case Report and Literature Review

AimsChronic mania is variably defined but classically recognized as the presence of manic symptoms for more than 2 years without remission. The reported incidence ranges between 6–15% among all patients with bipolar disorders. Although it has been described in psychiatry literature for a long time, it has not yet found a place in current nosological systemsMethodsWe present a 32-year-old single and unemployed man who is supported by his family and living with a sudden-onset, continuous illness of 12 years’ duration characterized by a resistant and markedly euphoric and expansive mood with grandiose delusions. Other features such as distractibility, pressured speech, racing thoughts and psychomotor disturbance remain significant but vary and are more responsive to medical interventions. Psychotic symptoms are largely confined to mood-congruent delusions, grandiose and religious, and are reported to have followed the mood disturbance from early on. There is no history of substance use, past psychiatric or medical illness, or head trauma and no evidence of a neurological cause on workup. This gentleman has been treated with a range of mood stabilizers and antipsychotics and two courses of ECT over the years. In the recent years, he has been on a combination of Clozapine, Valproate, and Pregabalin with relatively favorable but inadequate response and limited functional improvement.ResultsChronic mania lasting for 12 years, in the absence of an organic cause, despite the use of a wide gamut of modern psychotropics, alone and in combination with ECT, and with adequate compliance is an exceptionally rare entity. It poses manifold challenges both in terms of diagnostic considerations and therapeutic approaches. The overlap of symptoms of mania, schizophrenia, and schizoaffective disorders along with chronicity adds a particular layer of complexity. The hallmark of chronic mania is euphoric and expansive mood along with grandiose delusions and the presentation is relatively less centered on sleep disturbance, hypersexuality, and psychomotor agitation as compared to an acute manic episode. It is distinguished from schizophrenia spectrum disorders as it lacks flat or inappropriate affect, incongruent delusions and disorganized thought. Course of illness, prior mood episodes and family history are important in differentiating from a schizoaffective pattern of disease.ConclusionUnremitting mania of this duration is unique in its psychiatric morbidity and devastating in its impact on the individual in terms of psychosocial functioning, quality of life, physical health and safety. It also brings unprecedented stress on the family and other support systems.

Neuromolecular Etiology of Bipolar Disorder: Possible Therapeutic Targets of Mood Stabilizers.

Bipolar disorder is a mental illness that causes extreme mood swings and has a chronic course. However, the mechanism by which mood episodes with completely opposite characteristics appear repeatedly, or a mixture of symptoms appears, in patients with bipolar disorder remains unknown. Therefore, mood stabilizers are indicated only for single mood episodes, such as manic episodes and depressive episodes, and no true mood-stabilizing drugs effective for treating both manic and depressive episodes currently exist. Therefore, in this review, therapeutic targets that facilitate the development of mood stabilizers were examined by reviewing the current understanding of the neuromolecular etiology of bipolar disorder.

Pharmacological Management of Bipolar Disorder

Bipolar disorder is a mental pathology that has been known since ancient times and has its origin in the concept of “mania,” a term that comes from the Greek “µανια,” meaning “madness” or “frenzy”. Bipolar II is a history of at least one hypomanic episode plus at least one episode of major depression. Drug treatment for bipolar disorder has three symptom targets such as manic symptoms, mixed episodes, or depression and is usually given in stages. Lithium salts showed great efficacy in the treatment of manic disorder and they did so in a short period of time within several days. Lithium is the drug of choice in treating recurrent bipolar affective disorder (i.e., manic-depressive illness). Lithium was also relatively effective in treating manic manifestations in early dementia.

False dogmas in mood disorders research: Towards a nomothetic network approach.

The current understanding of major depressive disorder (MDD) and bipolar disorder (BD) is plagued by a cacophony of controversies as evidenced by competing schools to understand MDD/BD. The DSM/ICD taxonomies have cemented their status as the gold standard for diagnosing MDD/BD. The aim of this review is to discuss the false dogmas that reign in current MDD/BD research with respect to the new, data-driven, machine learning method to model psychiatric illness, namely nomothetic network psychiatry (NNP). This review discusses many false dogmas including: MDD/BD are mind-brain disorders that are best conceptualized using a bio-psycho-social model or mind-brain interactions; mood disorders due to medical disease are attributable to psychosocial stress or chemical imbalances; DSM/ICD are the gold standards to make the MDD/BD diagnosis; severity of illness should be measured using rating scales; clinical remission should be defined using threshold values on rating scale scores; existing diagnostic BD boundaries are too restrictive; and mood disorder spectra are the rule. In contrast, our NNP models show that MDD/BD are not mind-brain or psycho-social but systemic medical disorders; the DSM/ICD taxonomies are counterproductive; a shared core, namely the reoccurrence of illness (ROI), underpins the intertwined recurrence of depressive and manic episodes and suicidal behaviors; mood disorders should be ROI-defined; ROI mediates the effects of nitro-oxidative stress pathways and early lifetime trauma on the phenome of mood disorders; severity of illness and treatment response should be delineated using the NNP-derived causome, pathway, ROI and integrated phenome scores; and MDD and BD are the same illness.

A false positive fentanyl result on urine drug screen in a patient treated with ziprasidone

BackgroundThe objective of this case report is to highlight the possibility of the second-generation antipsychotic ziprasidone causing a false positive result for fentanyl on a urine drug screen (UDS). Case summaryA 70-year-old female was admitted to an inpatient psychiatric unit for treatment of a manic episode of bipolar I disorder. She had no previous history of a substance use disorder (SUD) and had no previous positive results on UDS tests spanning an 8-year period. However, her UDS obtained in the emergency department (ED) was positive for fentanyl. The patient adamantly denied that she had ingested anything other than her prescribed medications. Her outpatient psychiatric provider also endorsed that she had no previous known history of an SUD. It was suspected that the patient’s treatment with ziprasidone prior to admission and in the ED contributed to this positive fentanyl result. Practice implicationsIt has been established that risperidone may cause false positive fentanyl results on UDS. Due to structural similarities, ziprasidone may also cause this same result. As clinicians become more aware of the ubiquity of fentanyl in the illicit drug supply, it is imperative that clinicians also consider limitations of the currently available UDSs.

Cariprazine Use in Combination With a Mood Stabilizer in First Episode Mania.

BackgroundCariprazine's efficacy and safety have been previously tested in adult patients with acute mania associated with bipolar I disorder, but there is no available data in FEM. The objective of this study is to assess the efficacy and safety of cariprazine in combination with a mood stabilizer in treating FEM as well as to evaluate patients' adherence to the treatment.MethodsFEM patients were recruited from the acute inpatient unit at Lleida University Hospital Santa Maria, between January and June 2021. Their symptoms were evaluated using the Young Mania Rating Scale (YMRS) and the Clinical Global Impressions–Severity (CGI-S) scale at admission and at discharge. Akathisia was assessed using the Barnes Akathisia Rating Scale. Patient adherence to medication treatment was assessed 30 days after discharge using the Morisky, Green and Levine Medication Adherence Scale. Socio-demographic and clinical information were further collected.ResultsEleven patients with FEM were involved, seven women and four men. Their mean age was 26.00+/-6.37 years. Mean hospitalization was 17.36+/−4.7 days. Cariprazine was combined with a mood stabilizer: lithium in seven patients and divalproex in four. Mean YMRS change from baseline was −24.55+/−7.5 and the mean CGI-S change from baseline was −2.55+/−0.82. Regarding adverse events, two (18.2%) patients presented with akathisia. At the 30-day treatment-adherence assessment, six (54.5%) patients were adherent and four (36.4%) had moderate adherence.ConclusionIn this sample, cariprazine in combination with mood stabilizers proved to be safe and effective in the treatment of FEM with more than half the patients being adherent to treatment. Therefore, cariprazine add-on is a good choice for promoting the long-term adherence of patients, thus minimizing the risk of relapse and improving prognosis.

Assessment of cardiorespiratory fitness and physiological responses with different ergometers in people with bipolar disorder: data from the FINEXT-BD study

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Instituto de Salud Carlos III Background Bipolar disorder (BD) is a mental illness in which manic and depressive episodes are combined. People with BD are associated with an unhealthy lifestyle. Assessment of cardiorespiratory fitness (CRF) indicates the overall health of the person and is essential for the design of the exercise intensity ranges in an individualized way. The assessment of CRF can be performed with different ergometers (treadmill, T vs. cycloergometer, C) and the results may differ. Purpose To analyze and compare the CRF and physiological responses of two peak, progressive and ramped protocols on different ergometers (T and C) in people with BD. Methods Physiological variables (peak blood pressure, test duration, ventilatory threshold, peak heart rate, peak oxygen uptake [VO2peak], peak metabolic equivalent) assessed by cardiopulmonary exercise tests (T and C) were measured in participants (n=28, 67.8% women, 45.9±12.5 yr old) with BD. Results Differences were found in peak systolic blood pressure (T=148±29.5 vs. C=184±32.7 mmHg, P<0.001, Cohen's d=1.14), peak diastolic blood pressure (T=79±10.7 vs. v=88±17.1 mmHg, P<0.01, Cohen's d=0.72) and test duration (C=9.4±3.6 vs. T=11.3±4.9 min, P<0.01, Cohen's d=0.43) with higher values in C (24.5%, 12.4% and 19.6%, respectively). No other statistically significant (P>0.05) between ergometers-differences were found in the rest of studied variables, including VO2peak as the gold standard of CRF assessment (T=23.8±7.6 vs. C=24.6±7.7 mL·kg-1·min-1). Conclusions The no differences between ergometers (T vs. C) when assessing CRF and physiological responses in people with BD indicate that both modes of assessment could be used interchangeably. The increased blood pressure response in C compared to T could be due to unfamiliarity with the ergometer and the physiological factors that determine blood pressure.

Assessing positive and negative valence systems to refine animal models of bipolar disorders: the example of GBR 12909-induced manic phenotype.

Bipolar disorders are defined by recurrences of depressive and manic episodes. The pathophysiology is still unknown, and translating clinical symptoms into behaviors explorable in animal models is challenging. Animal models of bipolar disorder do not exist because cyclicity of the disease is impossible to mimic, and it is therefore necessary to study mania and depression models separately. Beyond mood, emotional biases differentiate bipolar states in humans. Mania is associated with positive biases, e.g. emotional stimuli become more rewarding and less aversive, and the opposite for depression. We propose to assess behavioral hedonic responses to innately appetitive and aversive olfactory and gustatory cues in mice as proxies for the assigned emotional valence. A mania model is therefore supposed to exhibit positive hedonic bias. Using the GBR 12909 mania model, we observed the classical hyperactivity phenotype, along with low depressive-like but high anxiety-like behaviors. Unexpectedly, GBR 12909-treated mice exhibited strong negative hedonic biases. Consequently, the GBR 12909 model of mania might not be appropriate for studying emotional disturbances associated with mania states. We propose olfactory and gustatory preference tests as crucial assessment for positive and negative valence biases, necessary for precisely characterizing animal models of bipolar disorders.

Differential expression of gene co-expression networks related to the mTOR signaling pathway in bipolar disorder

Bipolar disorder (BPD) is a severe mental illness characterized by episodes of depression and mania. To investigate the molecular mechanisms underlying the pathophysiology of bipolar disorder, we performed transcriptome studies using RNA-seq data from the prefrontal cortex (PFC) of individuals with BPD and matched controls, as well as data from cell culture and animal model studies. We found 879 differentially expressed genes that were also replicated in an independent cohort of post-mortem samples. Genes involving the mechanistic target of rapamycine (mTOR) pathway were down-regulated, while genes interrelated with the mTOR pathway such as Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway were up-regulated. Gene co-expression network analyses identified a module related to the mTOR pathway that was up-regulated in BPD and also enriched for markers of endothelial cells. We also found a down-regulated co-expression module enriched for genes involved in mTOR signalling and in mTOR related pathways and enriched with neuronal markers. The mTOR related modules were also replicated in the independent cohort of samples. To investigate whether the expression of the modules related to mTOR signalling pathway could be differentially regulated in different cell types we performed comparative network analyses in experimental models. We found both up-regulated modules in the PFC significantly overlapped with an up-regulated module in the brain endothelial cells from mice treated with lipopolysaccharides (LPS) and mTOR related pathways such as JAK-STAT, PI3K-Akt and ribosome were enriched in the common genes. In addition, the down-regulated module in the PFC significantly overlapped with a down-regulated module from neurons treated with the mTOR inhibitor, Torin1 and mTOR signalling, autophagy, and synaptic vesicle cycles were significantly enriched in the common genes. These results suggest that co-expression networks related to mTOR signalling pathways may be up- or down-regulated in different cell types in the PFC of BPD. These results provide novel insights into the molecular mechanisms underlying the pathophysiology of BPD.

Relationship of free thyroxine and triiodothyronine on recurrence in maintenance therapy for bipolar depression.

To examine whether thyroid function in the normal range is associated with recurrence of depressive or mania in bipolar disorder patients. 104 patients with bipolar disorder in maintenance therapy phase were assigned randomly to mood stabilizer combined with antidepressant group or mood stabilizer group. There were 52 patients in both groups respectively. Clinical symptoms were assessed at baseline, 3rd month, 6th month, 9th month, and 12th month using HAMD-17 and YMRS. Blood samples were analyzed for thyroid function. There was no statistically significant difference of recurrence rate of depressive episode and mania episode at the end of the 12-months between mood stabilizer combined with antidepressant group and mood stabilizer group. There was significant relation of baseline TT4 (P=0.020, HR = 0.948), FT3 (P=0.035, HR = 2.055), and FT4 (P=0.047, OR=0.769) with the recurrence of depressive episode in mood stabilizer group. The area under curve (AUC) of TT4, FT3, FT4 were 0.685, 0.613, 0.544, respectively. There was significant relation of baseline FT3 (P=0.044，HR = 4.493) with the recurrence of mania episode for mood stabilizer combined with antidepressants group. The AUC of FT3 was 0.806. Low level of TT4, FT4 and high level of FT3 within normal-range were related with the recurrence of depressive episode in the maintenance treatment with mood stabilizer of bipolar disorder. High level of FT3 within normal-range were related with recurrence of mania when mood stabilizer combined with antidepressants were used in the maintenance treatment of bipolar disorder.

Age at the onset of a first episode of psychotic mania is not a determinant of short-term outcome in a specialised early psychosis treatment setting

Age at the onset of a first episode of psychotic mania is not a determinant of short-term outcome in a specialised early psychosis treatment setting

Med Check: Adlarity Transdermal Patch; Qulipta; Nuplazid; and More

Back to table of contents Previous article Next article Med CheckFull AccessMed Check: Adlarity Transdermal Patch; Qulipta; Nuplazid; and MoreTerri D’ArrigoTerri D’ArrigoSearch for more papers by this authorPublished Online:26 Apr 2022https://doi.org/10.1176/appi.pn.2022.05.5.35Adlarity Transdermal Patch Approved for Treatment of Alzheimer’sIn March the U.S. Food and Drug Administration (FDA) approved Adlarity (donepezil transdermal system) as a treatment for patients with mild, moderate, or severe dementia associated with Alzheimer’s disease, Corium Inc. announced. Adlarity is a once-weekly patch that continuously delivers either 5 mg or 10 mg of donepezil through the skin per day. Either the patient or a caregiver may place the patch on the patient’s back, thigh, or buttocks.The FDA approved Adlarity based on a relative bioavailability study in healthy patients that compared the transdermal system to Aricept (donepezil hydrochloride) tablets. In the study, 60 healthy volunteers received 5 mg of Adlarity per day for five weeks, after which they received either 10 mg of Adlarity or oral donepezil per day for another five weeks. At the end of the study, exposure to donepezil was similar among patients who took Adlarity and those who took oral donepezil. Adlarity is expected to be available in the early fall. Qulipta Promising for Treatment of Chronic MigraineAdults with chronic migraine who took Qulipta (atogepant) in a phase 3 trial experienced fewer monthly migraine days compared with those who took placebo, AbbVie announced in March. Qulipta is currently approved for preventing episodic migraine in adults.In the trial, more than 750 patients with at least a one-year history of chronic migraine were randomized to receive 60 mg of atogepant once a day, 30 mg of atogepant twice a day, or placebo for 12 weeks. All patients had at least 15 headache days with at least eight migraine days in the 28 days before randomization. The trial consisted of two analyses based on regulatory agency feedback in the United States and European Union.The U.S. analysis revealed that patients in the 60 mg and 30 mg atogepant arms experienced a decrease of 6.88 and 7.46 monthly migraine days, respectively, compared with patients in the placebo arm, who experienced a decrease of 5.05 monthly migraine days. The European Union analysis revealed that patients in the 60 mg and 30 mg atogepant arms experienced a decrease of 6.75 and 7.33 monthly migraine days, respectively, compared with patients in the placebo arm, who experienced a decrease of 5.09 monthly migraine days. Acadia Resubmits Nuplazid for Treatment of Alzheimer’s PsychosisAcadia Pharmaceuticals in March announced that the FDA has set an action date for the company’s resubmitted supplemental New Drug Application (sNDA) for Nuplazid (pimavanserin) for the treatment of hallucinations and delusions associated with Alzheimer’s disease psychosis. The FDA’s Division of Psychiatry has also advised the company that it is planning to hold an advisory committee meeting in connection with its review.In April 2021 the FDA rejected pimavanserin for this indication, citing “a lack of statistical significance in some of the subgroups of dementia, and insufficient numbers of patients with certain less common dementia subtypes as lack of substantial evidence of effectiveness to support approval.”The resubmission provides additional analyses from two previously conducted clinical studies, HARMONY and Study-019, to support the proposed indication for the drug and addresses the issues raised in the FDA’s rejection last year.Pimavanserin is currently approved for the treatment of hallucinations and delusions associated with Parkinson’s disease psychosis. Vraylar sNDA Submitted for Adjunctive Treatment of Major Depressive DisorderIn February AbbVie announced that it has submitted an sNDA for Vraylar (cariprazine) for the adjunctive treatment of major depressive disorder in patients who are receiving ongoing antidepressant therapy. Cariprazine is currently approved for the treatment of schizophrenia in adults, the acute treatment of manic or mixed episodes associated with bipolar I disorder in adults, and the treatment of depressive episodes associated with bipolar I disorder in adults.In a phase 3 study of 759 adults with major depressive disorder, patients who took 1.5 mg cariprazine daily experienced a statistically significant change from baseline to week six in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score compared with those who took placebo. In a second study, patients who took 2 mg to 4.5 mg of cariprazine per day also experienced a significant change from baseline to week eight in the MADRS total score compared with those who took placebo. In both of these studies, no new safety events were identified. ■ ISSUES NewArchived

Sexually transmitted infections in sexually compulsive women

ABSTRACT Introduction There is a large evidence in literature associating compulsive sexual behavior (CSB) with negative outcomes, including increased risk of sexually transmitted infections (STI), unwanted pregnancies, work or educational role impairment, excessive financial expenses, and others. Most research supports that CSB is substantially more frequent among men than women, which could explain the paucity of data about distribution, accurate clinical picture and particularities in this population. Objective we proposed an investigation of lifetime reported serological tests and STI in women who are outpatients of a compulsive sexual behavior clinic in Sao Paulo, Brazil. Methods we conducted a cross-sectional analysis of data from women who sought treatment in the clinic between 2012 to 2019. Participants are submitted by throughout clinical evaluation to assessing sexual compulsivity severity. Data of lifetime STI, previous treatment and serological tests are asked by a semi-structured interview. The participants who met diagnostic criteria for sexual preference disorder, sexual identity disorder, schizophrenia or other psychotic disorders, hypomanic or manic episode of mood disorder and other mental disorders due to brain dysfunction, injury or physical illness were excluded. Results thirty-two women completed baseline evaluation. Of this, twenty-two (68%) met criteria to CSB and twelve (32%) did not. There was no difference in mean of age, proportion of sexual orientation, race, marital status, years of education or income (TABLE 1). Most of women were white, heterosexual and weren't in a stable relationship. The median (Md) of Sexual Compulsivity Scale (SCS) score had significant difference (Md 32,5 IQR [26; 36] to sexually compulsive and Md 11,5 IQR [10,5; 14] to non sexually compulsive; p<0.05) (TABLE 2). Self-reported history of STI was present in 40% of compulsive women while 8% of non-compulsive reported it (p 0.75). About 91% of compulsive and 75% of non-compulsive women reported previous serological tests. Conclusion Sexually compulsive women reported more STI than non sexually compulsive women. We believe that small sample size was determinant to do not find statistical difference between the groups due the low statistical power of the test. Further research with greater sample is needed to confirm this inference. However, sexually compulsive women presented high severity of sexual compulsivity which support our inference. The study points out to the importance of psychiatrist to assess STI in sexually compulsive women. Disclosure Work supported by industry: no.

P167. Association of Wnt7a Pathways in Distinct Human Amygdala Cell Populations and Affective Symptoms in Bipolar Disease

Bipolar disorder (BD) is defined by episodes of mania (appetitive drive for reward and pleasure) alternating with depression, anxiety and reduced appetitive drive. There is strong evidence that distinct neuronal circuits driven by specific cell population in the amygdala are key players in aversive and appetitive behavior. These neuronal populations express selective members of the Wnt pathway, specifically Wnt7a and its downstream regulators. Lithium, a classical mood stabilizer, inhibits GSK3β, one of the Wnt downstream family members.

P178. Heart Rate Variability as Biomarker for Bipolar Mania

Bipolar disorder (BD) is characterized by alterations in mood, energy, motor activity, and the ability to function. The depressed state is associated with dysfunction in the autonomic nervous system (ANS), indexed by heart rate variability (HRV). However, there are less consistent findings concerning ANS dysfunction in manic states. The main aim of the study was to investigate within-individual changes in HRV from manic to euthymic states in bipolar disorder (BD).

Effect of Probiotic Supplements on Oxidative Stress Biomarkers in First-Episode Bipolar Disorder Patients: A Randomized, Placebo-Controlled Trial.

Background: Currently no study has examined the effects of probiotic administration on the symptoms of anxiety, depression, and mania, as well as their correlations with the biomarkers of oxidative stress in patients with bipolar disorder (BPD). The aim of this study is to determine the effects of probiotic supplementation on plasma oxidative stress-related biomarkers and different domains of clinical symptom in patients suffering from BPD. Methods: Eighty first-episode drug-naive patients with BPD were recruited. The subjects were randomized to receive psychotropic drugs supplementing with either probiotic or placebo and scheduled to evaluate with follow-ups for clinical symptom improvements and changes in the oxidative stress biomarkers. The Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, and Young Mania Rating Scale were used to assess the clinical symptomatology. The panel of plasma oxidative stress biomarkers were determined by ultra-performance liquid chromatography–mass spectrometry (UPLC–MS/MS) at baseline and for 3 months of follow-up, i.e., at post-treatment month 1, 2, and 3. Results: After 3 months of intervention, decreased levels of plasma lysophosphatidylcholines (LPCs) were found in both placebo and probiotic groups. However, six other oxidative stress biomarkers (i.e., creatine, inosine, hypoxanthine, choline, uric acid, allantoic acid) increased in BPD patients after the two types of therapies. In addition, a positive correlation between changes of LPC (18:0) and YMRS scale was found in BPD patients and this association only existed in the probiotic group. Additionally, the mania symptom greatly alleviated (pretreatment–posttreatment, odds ratio = 0.09, 95%CI = 0.01, 0.64, p= 0.016) in patients who received probiotic supplements as compared with the placebo group. Conclusion: The changes in plasma biomarkers of oxidative stress in patients with BPD have a potential to be trait-like markers, and serve as prognostic indexes for bipolar patients. Daily intakes of probiotics have advantageous effects on BPD patients with certain clinical symptoms, especially manic symptoms. The treatment may be a promising adjunctive therapeutic strategy for BPD patients in manic episode.

Combination Olanzapine and Samidorphan for the Management of Schizophrenia and Bipolar 1 Disorder in Adults: A Narrative Review.

Schizophrenia is a debilitating psychotic disorder characterized by positive symptoms such as delusions, hallucinations, and disorganized thoughts, and negative symptoms like lack of effect or motivation. Bipolar 1 disorder (B1D) is a psychiatric illness characterized by recurrent manic episodes in alternation with depressive episodes and interspersed periods of euthymia, ultimately resulting in psychological distress and impairment of daily functioning. Effective treatments are needed for both schizophrenia and B1D to reach the treatment goals of reducing the debilitating symptomology, improving social functioning and quality of life, and increasing the chances of recovery and more favorable long-term outcomes. To date, olanzapine is one of the most efficacious atypical antipsychotics (AAPs) for the treatment of both schizophrenia and B1D and is associated with fewer extrapyramidal effects compared to other treatments. However, compared to other AAPs, olanzapine is associated with a greater chance of metabolic syndrome, limiting its clinical use and affecting treatment compliance. Samidorphan mitigates the weight gain side effects of olanzapine by antagonizing μ-, κ-, and δ-opioid receptors. The use of combination drugs to treat psychiatric conditions is an emerging field with the goal of increasing therapeutic efficacy and decreasing undesirable side effects. Clinical trials have demonstrated combination on olanzapine and samidorphan (OLZ/SAM) treatment resulted in significantly less weight gain than olanzapine monotherapy. Clinical trial patients reported improvements in symptoms of psychosis, reduced weight gain, and overall satisfaction with their treatment. OLZ/SAM has been as shown to be a safe and effective pharmaceutical option for the clinical management of schizophrenia and B1D.

Neutrophil/lymphocyte, platelet/lymphocyte and monocyte/lymphocyte ratios in patients with affective disorders

ObjectiveThere is substantial evidence to support that the alterations in the immune-inflammation system play a crucial role in the pathogenic mechanism of affective disorders. The neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR) and monocyte/lymphocyte ratio (MLR) have been recently investigated as simple, rapid, and inexpensive inflammation markers. The purpose of the research is to use large-scale clinical data to study the difference of the inflammation ratios in first-episode MDD, recurrent MDD, BD depressive episodes and manic episode. MethodsA cross-sectional design was applied to retrospectively analyse the data that were extracted from electronic health records. A total of 16,174 Chinese affective disorder patients were enrolled in this study, and 6681 healthy subjects served as controls. The differences in the NLR, MLR, PLR and whole blood count data among different groups were compared, and the contributing factors for the occurrence of MDD and BD were analysed. ResultsFirst-episode and recurrent MDD patients exhibited significantly elevated NLRs and MLRs compared to healthy controls. Compared with the MDD patients, the BD patients showed higher NLRs and MLRs and lower PLRs. Further analysis showed that the BD manic episode patients had significantly elevated NLRs and MLRs compared to patients with BD depressive episodes or MDD. MLR was a risk factor for the occurrence of MDD and that the NLR and MLR were risk factors for the occurrence of BD. ConclusionsOur study highlights the role of systemic inflammation in the pathophysiology of MDD and BD, particularly during manic BD episodes.