scholarly journals M147. ABERRANT TIMING AND ODDBALL DETECTION IN SCHIZOPHRENIA: FINDINGS FROM A TIME DISCRIMINATION / ODDBALL FMRI STUDY

2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S191-S191
Author(s):  
Javier Goena ◽  
María Sol Garcés ◽  
Irene Alústiza ◽  
Miguel Fernández-Martínez ◽  
María Fernández-Seara ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Cognitive Deficit ◽  
Bipolar Depression ◽  
Cognitive Profile ◽  
Salience Network ◽  
Time Processing ◽  
Time Discrimination ◽  
Brain Circuits ◽  
Fmri Study ◽  
The Brain

Abstract Background Schizophrenia (SZ) is associated with deficits in both temporal and salience processing. The underlying neurological dysfunctions in both processes, which are interrelated and share neuroanatomical bases, remain poorly understood. Our main objective is to examine the hypothesis that the dysfunction of the brain circuits involved in time and salience processing underlies the cognitive deficit of schizophrenia and, to a lesser extent, in bipolar disorder (BD). Methods 10 schizophrenia patients, 7 bipolar depression patients and 10 healthy volunteers carried out an original experimental test of TD/OD during fMRI brain scanning. All participants performed the MATRICS Consensus Cognitive Battery to assess their cognitive profile. Results We found that SZ patients showed hypoactivation in cortical and subcortical areas related both with time processing and Salience Network. The dysfunction observed during timing tasks partially coincided with deficiencies in Oddball tasks. Discussion A dysfunctional timing/salience detection network underlies the cognitive impairment observed in SZ but not in BD patients.

Staging and neuroprogression in bipolar disorder: treatment implications

2017 ◽  
Author(s):  
Ives Cavalcante Passos ◽  
Flávio Kapczinski
Keyword(s):  
Bipolar Disorder ◽  
Treatment Guidelines ◽  
Current Treatment ◽  
Behaviour Therapy ◽  
Brain Circuits ◽  
Cognitive Behaviour ◽  
Disorder Treatment ◽  
Clinical Questions ◽  
The Brain ◽  
Progressive Course

It is known that if, not all, a substantial proportion of patients with bipolar disorder (BD) present a progressive course with functional and cognitive impairment. In addition, patients with BD and multiple mood episodes have a worse response to lithium and cognitive behaviour therapy. However, many current treatment guidelines do not take these clinical features that change with illness progression into account. In order to clarify these clinical questions, the term ‘neuroprogression’ was conceptualized as the pathological rewiring of the brain that takes place in parallel with the clinical deterioration in the course of BD. It provides a heuristic basis for conceptualizing the biochemical foundation of changes in brain circuits related to the progressive course of BD. Herein, we aim to review risk factors, biological underpinnings, and treatment implications related to neuroprogression in BD.

Is the brain arachidonic acid cascade a common target of drugs used to manage bipolar disorder?

2009 ◽  
Vol 37 (5) ◽  
pp. 1104-1109 ◽  
Author(s):  
Richard P. Bazinet
Keyword(s):  
Bipolar Disorder ◽  
Valproic Acid ◽  
Arachidonic Acid ◽  
Rat Brain ◽  
Bipolar Depression ◽  
Chronic Administration ◽  
Mood Stabilizers ◽  
Arachidonic Acid Cascade ◽  
Brain Phospholipids ◽  
The Brain

Although lithium has been used therapeutically to treat patients with bipolar disorder for over 50 years, its mechanism of action, as well as that of other drugs used to treat bipolar disorder, is not agreed upon. In the present paper, I review studies in unanaesthetized rats using a neuropharmacological approach, combined with kinetic, biochemical and molecular biology techniques, demonstrating that chronic administration of three commonly used mood stabilizers (lithium, valproic acid and carbamazepine), at therapeutically relevant doses, selectively target the brain arachidonic acid cascade. Upon chronic administration, lithium and carbamazepine decrease the binding activity of activator protein-2 and, in turn, the transcription, translation and activity of its arachidonic acid-selective calcium-dependent phospholipase A2 gene product, whereas chronic valproic acid non-competitively inhibits long-chain acyl-CoA synthetase. The net overlapping effects of the three mood stabilizers are decreased turnover of arachidonic acid, but not of docosahexaenoic acid, in rat brain phospholipids, as well as decreased brain cyclo-oxygenase-2 and prostaglandin E2. As an extension of this theory, drugs that are thought to induce switching to mania, especially when administered during bipolar depression (fluoxetine and imipramine), up-regulate enzymes of the arachidonic acid cascade and turnover of arachidonic acid in rat brain phospholipids. Future basic and clinical studies on the arachidonic acid hypothesis of bipolar disorder are warranted.

Assessment of the neuronal underpinnings of cognitive impairment in bipolar disorder with a picture encoding paradigm and methodological lessons learnt

2021 ◽  
pp. 026988112110085
Author(s):  
JZ Petersen ◽  
J Macoveanu ◽  
HL Kjærstad ◽  
GM Knudsen ◽  
LV Kessing ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Cognitive Impairment ◽  
Neuronal Activity ◽  
Cognitive Impairments ◽  
Hierarchical Cluster ◽  
Small Region ◽  
Middle Temporal Gyrus ◽  
Recall Accuracy ◽  
Fmri Study

Background: Mood disorders are often associated with persistent cognitive impairments. However, pro-cognitive treatments are essentially lacking. This is partially because of poor insight into the neurocircuitry abnormalities underlying these deficits and their change with illness progression. Aims: This functional magnetic resonance imaging (fMRI) study investigates the neuronal underpinnings of cognitive impairments and neuronal change after mood episodes in remitted patients with bipolar disorder (BD) using a hippocampus-based picture encoding paradigm. Methods: Remitted patients with BD ( n=153) and healthy controls ( n=52) were assessed with neuropsychological tests and underwent fMRI while performing a strategic picture encoding task. A subgroup of patients ( n=43) were rescanned after 16 months. We conducted data-driven hierarchical cluster analysis of patients’ neuropsychological data and compared encoding-related neuronal activity between the resulting neurocognitive subgroups. For patients with follow-up data, effects of mood episodes were assessed by comparing encoding-related neuronal activity change in BD patients with and without episode(s). Results: Two neurocognitive subgroups were revealed: 91 patients displayed cognitive impairments while 62 patients were cognitively normal. No neuronal activity differences were observed between neurocognitive subgroups within the dorsal cognitive control network or hippocampus. However, exploratory whole-brain analysis revealed lower activity within a small region of middle temporal gyrus in impaired patients, which significantly correlated with poorer neuropsychological performance. No changes were observed in encoding-related neuronal activity or picture recall accuracy with the occurrence of mood episode(s) during the follow-up period. Conclusion: Memory encoding fMRI paradigms may not capture the neuronal underpinnings of cognitive impairment or effects of mood episodes.

scholarly journals Treatment of bipolar depression with supraphysiologic doses of levothyroxine: a randomized, placebo-controlled study of comorbid anxiety symptoms

2019 ◽  
Vol 7 (1) ◽  
Author(s):  
Maximilian Pilhatsch ◽  
Thomas J Stamm ◽  
Petra Stahl ◽  
Ute Lewitzka ◽  
Anne Berghöfer ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Rating Scale ◽  
Bipolar Depression ◽  
Phenotypic Expression ◽  
Anxiety Symptoms ◽  
Controlled Study ◽  
Double Blind ◽  
Comorbid Anxiety ◽  
Depressed Patients ◽  
Depressive Episodes

Abstract Background Symptoms of anxiety co-occur in a variety of disorders including in depressive episodes of bipolar disorder and in patients with thyrotoxicosis. Treatment of refractory bipolar disorder with supraphysiologic doses of levothyroxine (L-T4) has been shown to improve the phenotypic expression of the disorder and is associated with an increase of circulating thyroid hormones. However, it might be associated with somatic and mental adverse effects. Here we report the investigation of the influence of treatment with supraphysiologic doses of L-T4 on symptoms of anxiety in patients with refractory bipolar depression. Methods Post-hoc analysis from a 6-week, multi-center, randomized, double-blind, placebo-controlled study of the effects of supraphysiologic L-T4 treatment on anxiety symptoms in bipolar depression. Anxiety symptoms were measured weekly with the Hamilton anxiety/somatization factor (HASF) score of the Hamilton Depression Rating Scale (HAMD) and the State- and Trait Anxiety Inventory (STAI). Results Treatment of both groups was associated with a significant reduction in anxiety symptoms (p < 0.001) with no statistical difference between groups (LT-4: from 5.9 (SD = 2.0) at baseline to 3.7 (SD = 2.4) at study end; placebo: from 6.1 (SD = 2.4) at baseline to 4.4 (SD = 2.8) at study end; p = 0.717). Severity of anxiety at baseline did not show a statistically significant correlation to the antidepressive effect of treatment with supraphysiologic doses of L-T4 (p = 0.811). Gender did not show an influence on the reduction of anxiety symptoms (females: from 5.6 (SD = 1.7) at baseline to 3.5 (SD = 2.4) at study end; males: from 6.1 (SD = 2.3) at baseline to 4.0 (SD = 2.4) at study end; p = 0.877). Conclusions This study failed to detect a difference in change of anxiety between bipolar depressed patients treated with supraphysiologic doses of L-T4 or placebo. Comorbid anxiety symptoms should not be considered a limitation for the administration of supraphysiologic doses of L-T4 refractory bipolar depressed patients. Trial registration ClinicalTrials, ClinicalTrials.gov identifier: NCT01528839. Registered 2 June 2012—Retrospectively registered, https://clinicaltrials.gov/ct2/show/study/NCT01528839

Prescribing practices of Indian psychiatrists in the treatment of bipolar disorder

2019 ◽  
Vol 53 (5) ◽  
pp. 458-469 ◽  
Author(s):  
YC Janardhan Reddy ◽  
Venugopal Jhanwar ◽  
Rajesh Nagpal ◽  
MS Reddy ◽  
Nilesh Shah ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Maintenance Treatment ◽  
Bipolar Depression ◽  
Mood Stabilizer ◽  
Self Report ◽  
Mood Stabilizers ◽  
Prescribing Practices ◽  
Term Outcome ◽  
Cross Sectional ◽  
Long Term Outcome

Objective: The treatment of bipolar disorder is challenging because of its clinical complexity and availability of multiple treatment options, none of which are ideal mood stabilizers. This survey studies prescription practices of psychiatrists in India and their adherence to guidelines. Method: In total, 500 psychiatrists randomly selected from the Indian Psychiatric Society membership directory were administered a face-to-face 22-item questionnaire pertaining to the management of bipolar disorder. Results: For acute mania, most practitioners preferred a combination of a mood stabilizer and an atypical antipsychotic to monotherapy. For acute depression, there was a preference for a combination of an antidepressant and a mood stabilizer over other alternatives. Electroconvulsive therapy was preferred in the treatment of severe episodes and to hasten the process of recovery. Approximately, 50% of psychiatrists prescribe maintenance treatment after the first bipolar episode, but maintenance therapy was rarely offered lifelong. While the majority (85%) of psychiatrists acknowledged referring to various clinical guidelines, their ultimate choice of treatment was also significantly determined by personal experience and reference to textbooks. Limitations: The study did not study actual prescriptions. Hence, the responses to queries in the survey are indirect measures from which we have tried to understand the actual practices, and of course, these are susceptible to self-report and social-desirability biases. This was a cross-sectional study; therefore, temporal changes in responses could not be considered. Conclusion: Overall, Indian psychiatrists seemed to broadly adhere to recommendations of clinical practice guidelines, but with some notable exceptions. The preference for antidepressants in treating depression is contrary to general restraint recommended by most guidelines. Therefore, the efficacy of antidepressants in treating bipolar depression in the context of Indian psychiatrists’ practice needs to be studied systematically. Not initiating maintenance treatment early in the course of illness may have serious implications on the long-term outcome of bipolar disorder.

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