scholarly journals Dentate gyrus activin signaling mediates the antidepressant response

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mark M. Gergues ◽  
Christine N. Yohn ◽  
Anusha Bharadia ◽  
Marjorie R. Levinstein ◽  
Benjamin Adam Samuels
Keyword(s):  
Dentate Gyrus ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Neural Circuit ◽  
Antidepressant Treatment ◽  
Treatment Resistance ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Activin Signaling ◽  
Antidepressant Treatments ◽  
Chronic Social Defeat Stress

AbstractAntidepressants that target monoaminergic systems, such as selective serotonin reuptake inhibitors (SSRIs), are widely used to treat neuropsychiatric disorders including major depressive disorder, several anxiety disorders, and obsessive-compulsive disorder. However, these treatments are not ideal because only a subset of patients achieve remission. The reasons why some individuals remit to antidepressant treatments while others do not are unknown. Here, we developed a paradigm to assess antidepressant treatment resistance in mice. Exposure of male C57BL/6J mice to either chronic corticosterone administration or chronic social defeat stress induces maladaptive affective behaviors. Subsequent chronic treatment with the SSRI fluoxetine reverses these maladaptive affective behavioral changes in some, but not all, of the mice, permitting stratification into persistent responders and non-responders to fluoxetine. We found several differences in expression of Activin signaling-related genes between responders and non-responders in the dentate gyrus (DG), a region that is critical for the beneficial behavioral effects of fluoxetine. Enhancement of Activin signaling in the DG converted behavioral non-responders into responders to fluoxetine treatment more effectively than commonly used second-line antidepressant treatments, while inhibition of Activin signaling in the DG converted responders into non-responders. Taken together, these results demonstrate that the behavioral response to fluoxetine can be bidirectionally modified via targeted manipulations of the DG and suggest that molecular- and neural circuit-based modulations of DG may provide a new therapeutic avenue for more effective antidepressant treatments.

scholarly journals Dentate Gyrus Activin Signaling Mediates the Antidepressant Treatment Response

2018 ◽  
Author(s):  
Mark M Gergues ◽  
Christine N Yohn ◽  
Marjorie R Levinstein ◽  
Benjamin Adam Samuels
Keyword(s):  
Dentate Gyrus ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Neural Circuit ◽  
Antidepressant Treatment ◽  
Treatment Resistance ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Activin Signaling ◽  
Negative Valence ◽  
Antidepressant Treatments

Antidepressants that target monoaminergic systems, such as selective serotonin reuptake inhibitors (SSRIs), are widely used to treat neuropsychiatric disorders including major depressive disorder, several different anxiety disorders, and obsessive-compulsive disorder. However, these treatments are not ideal because only a subset of patients achieve remission. The reasons why some individuals remit to antidepressant treatments while others do not are unknown. Here, we developed a paradigm to assess antidepressant treatment resistance in mice. Treatment of mice with either chronic corticosterone or chronic social defeat stress effectively induces increased negative valence behaviors. Subsequent chronic treatment with the SSRI fluoxetine reverses these behavioral changes in some, but not all, of the mice, permitting stratification into persistent responders and non-responders to fluoxetine. We found several significant differences in expression of Activin signaling-related genes between responders and non-responders to fluoxetine in the dentate gyrus, a region that we recently reported is critical for the beneficial behavioral effects of fluoxetine. Furthermore, enhancement of Activin signaling in the dentate gyrus converted behavioral non-responders into responders to fluoxetine treatment more effectively than commonly used adjunctive antidepressant treatments, while inhibition of Activin signaling in the dentate gyrus converted responders into non-responders. Taken together, these results demonstrate that the behavioral response to FLX can be bidirectionally modified via targeted manipulations of the dentate gyrus and suggest that molecular- and neural circuit-based modulations of dentate gyrus may provide a new therapeutic avenue for more effective antidepressant treatments or adjunctive therapies.

scholarly journals Voxel-wise meta-analysis of grey matter changes in obsessive–compulsive disorder

2009 ◽  
Vol 195 (5) ◽  
pp. 393-402 ◽  
Author(s):  
Joaquim Radua ◽  
David Mataix-Cols
Keyword(s):  
Obsessive Compulsive Disorder ◽  
Grey Matter ◽  
Antidepressant Treatment ◽  
Meta Analysis ◽  
Anterior Cingulate ◽  
Control Group ◽  
Grey Matter Volume ◽  
Obsessive Compulsive ◽  
Caudate Nuclei ◽  
Compulsive Disorder

BackgroundSpecific cortico-striato-thalamic circuits are hypothesised to mediate the symptoms of obsessive–compulsive disorder (OCD), but structural neuroimaging studies have been inconsistent.AimsTo conduct a meta-analysis of published and unpublished voxel-based morphometry studies in OCD.MethodTwelve data-sets comprising 401 people with OCD and 376 healthy controls met inclusion criteria. A new improved voxel-based meta-analytic method, signed differential mapping (SDM), was developed to examine regions of increased and decreased grey matter volume in the OCD group v. control group.ResultsNo between-group differences were found in global grey matter volumes. People with OCD had increased regional grey matter volumes in bilateral lenticular nuclei, extending to the caudate nuclei, as well as decreased volumes in bilateral dorsal medial frontal/anterior cingulate gyri. A descriptive analysis of quartiles, a sensitivity analysis as well as analyses of subgroups further confirmed these findings. Meta-regression analyses showed that studies that included individuals with more severe OCD were significantly more likely to report increased grey matter volumes in the basal ganglia. No effect of current antidepressant treatment was observed.ConclusionsThe results support a dorsal prefrontal–striatal model of the disorder and raise the question of whether functional alterations in other brain regions commonly associated with OCD, such as the orbitofrontal cortex, may reflect secondary compensatory strategies. Whether the reported differences between participants with OCD and controls precede the onset of the symptoms and whether they are specific to OCD remains to be established.

scholarly journals Personality traits and treatment outcome in obsessive-compulsive disorder

2008 ◽  
Vol 30 (3) ◽  
pp. 246-250 ◽  
Author(s):  
Felipe Corchs ◽  
Fábio Corregiari ◽  
Ygor Arzeno Ferrão ◽  
Tania Takakura ◽  
Maria Eugênia Mathis ◽  
...  
Keyword(s):  
Treatment Outcome ◽  
Personality Traits ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Behavioral Therapy ◽  
Temperament And Character Inventory ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Scale Scores ◽  
Character Inventory ◽  
Poor Treatment

OBJECTIVE: Comorbidity with personality disorders in obsessive-compulsive patients has been widely reported. About 40% of obsessive-compulsive patients do not respond to first line treatments. Nevertheless, there are no direct comparisons of personality traits between treatment-responsive and non-responsive patients. This study investigates differences in personality traits based on Cloninger's Temperament and Character Inventory scores between two groups of obsessive-compulsive patients classified according to treatment outcome: responders and non-responders. METHOD: Forty-four responsive and forty-five non-responsive obsessive-compulsive patients were selected. Subjects were considered treatment-responsive (responder group) if, after having received treatment with any conventional therapy, they had presented at least a 40% decrease in the initial Yale-Brown Obsessive Compulsive Scale score, had rated "better" or "much better" on the Clinical Global Impressions scale; and had maintained improvement for at least one year. Non-responders were patients who did not achieve at least a 25% reduction in Yale-Brown Obsessive Compulsive Scale scores and had less than minimal improvement on the Clinical Global Impressions scale after having received treatment with at least three selective serotonin reuptake inhibitors (including clomipramine), and at least 20 hours of cognitive behavioral therapy. Personality traits were assessed using Temperament and Character Inventory. RESULTS: Non-responders scored lower in self-directedness and showed a trend to score higher in persistence than responders did. CONCLUSION: This study suggests that personality traits, especially self-directedness, are associated with poor treatment response in obsessive-compulsive patients.

Treatment Resistance in Obsessive-Compulsive Disorder

2018 ◽  
pp. 165-177 ◽  
Author(s):  
Rachel Middleton ◽  
Michael G. Wheaton ◽  
Reilly Kayser ◽  
H. Blair Simpson
Keyword(s):  
Obsessive Compulsive Disorder ◽  
Treatment Resistance ◽  
Obsessive Compulsive ◽  
Compulsive Disorder

Coprophagia in an Elderly Man: A Case Report and Review of the Literature

2005 ◽  
Vol 35 (4) ◽  
pp. 417-427 ◽  
Author(s):  
David A. Beck ◽  
Nora R. Frohberg
Keyword(s):  
Mental Retardation ◽  
Behavioral Interventions ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Cerebral Atrophy ◽  
Laboratory Evaluation ◽  
Psychiatric Evaluation ◽  
Obsessive Compulsive ◽  
Supportive Psychotherapy ◽  
Compulsive Disorder ◽  
Medical Disorders

Objective: Coprophagia or the ingestion of feces has long been associated with psychiatric illness. It is considered to be a variant of pica. This behavior requires an extensive medical and psychiatric differential diagnosis. Medical disorders associated with coprophagia include seizure disorders, cerebral atrophy, and tumors. Psychiatric disorders associated with coprophagia include mental retardation, alcoholism, depression, obsessive compulsive disorder, schizophrenia, fetishes, delirium, and dementia. In animals, coprophagia is associated with boredom, thiamine deficiency, and lesions of the amygdala. Methods: A case of coprophagia in an elderly man is reported here. A 77-year-old man with mild mental retardation was referred for urgent psychiatric evaluation due to coprophagia. The case is discussed and the literature reviewed. Results: Psychiatric evaluation revealed cognitive dysfunction and depression. Physical examination and laboratory evaluation were noncontributory. He was started on sertraline 25 mg daily with resolution of his coprophagia. Coprophagia has been treated using behavioral interventions, supportive psychotherapy, elemental diets, tricyclic antidepressants, carbamazepine, haloperidol, and electroconvulsive therapy. Conclusions: Use of Selective Serotonin Reuptake Inhibitors (SSRIs) may also be an effective treatment for coprophagia, particularly in the setting of depression or anxiety.

Role of serotonin in obsessive-compulsive disorder

1998 ◽  
Vol 173 (S35) ◽  
pp. 13-20 ◽  
Author(s):  
H. G. Baumgarten ◽  
Z. Grozdanovic
Keyword(s):  
Obsessive Compulsive Disorder ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Expression Patterns ◽  
Term Treatment ◽  
Continuous Treatment ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Long Term Treatment ◽  
Pre Treatment

Background Serotonin may play a role in the pathophysiology of obsessive-compulsive disorder (OCD) because of the anti-obsessional effect of selective serotonin reuptake inhibitors (SSRJs).Method The literature is reviewed on knowledge of the role of serotonergic neurons in brain function, studies on monoamine metabolites in cerebrospinal fluid (CSF), various stress neuropeptides, neuroendocrine and behavioural challenge after administration of direct and indirect serotomimetic compounds, and neuroanatomical data on brain circuits organising behaviour.Results In most of the OCD cases analysed, CSF 5-hydroxyindoleacetic acid and homovanillic acid concentrations do not significantly differ from age-corrected controls. However, a relationship appears to exist between pre-treatment levels of these metabolites and clinical response to drugs acting on the serotonin transporter. Abnormalities in CSF arginine vasopressin, corticotropin-releasing hormone, oxytocin and somatostatin levels have been reported in OCD. Long-term treatment with high-doses of clomipramine, fluvoxamine, and fluoxetine tend to correct these neuropeptide abnormalities.Conclusions We hypothesise that continuous treatment with SSRJs alters serotonin turnover and neuropeptide expression patterns in OCD-entertaining functional forebrain/midbrain circuits.

Repeating, counting, and touching to prevent harm

2021 ◽  
pp. 137-142
Author(s):  
Ivana Viani
Keyword(s):  
Gold Standard ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Serotonin Reuptake Inhibitors ◽  
Repetitive Behaviors ◽  
Response Prevention ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Impairment In Functioning ◽  
Clinically Significant ◽  
Mental Acts

Obsessive-compulsive disorder (OCD) is characterized by obsessions and/or compulsions that are time-consuming or cause clinically significant distress or impairment in functioning. Obsessions are recurrent and persistent intrusive, unwanted thoughts, urges, or images that cause marked anxiety or distress. Examples of obsessions include worrying about germs, the feeling things need to be “just right,” worrying about bad things happening, and disturbing thoughts or images about hurting others. Compulsions are repetitive behaviors or mental acts that an individual feels compelled to perform in response to an obsession or according to rules that must be applied rigidly. Examples of compulsions include washing, checking, tapping, ordering, and repeating. Young children may not be able to articulate the aims of these repetitive behaviors or mental acts. Selective serotonin reuptake inhibitors (SSRIs) are the first-line class of medications used to treat OCD in children and adolescents. Exposure and response prevention (ERP) therapy is the gold standard psychotherapy treatment for OCD.

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