Boosting serotonin increases information gathering by reducing subjective cognitive costs

Serotonin is implicated in the valuation of aversive costs, such as delay or physical effort. However, its role in governing sensitivity to cognitive effort, for example deliberation costs during information gathering, is unclear. We show that week-long treatment with a serotonergic antidepressant enhances a willingness to gather information when trying to maximize reward. Using computational modelling, we show this arises from a diminished sensitivity to subjective deliberation costs during the sampling process. This result is consistent with the notion that serotonin alleviates sensitivity to aversive costs in a domain-general fashion, with implications for its potential contribution to a positive impact on motivational deficits in psychiatric disorders.

Symptom specificity of ayahuasca's effect on depressive symptoms

BackgroundAyahuasca's effects on symptoms of depression have generated considerable optimism. Clients frequently report more concern about some symptoms than others, and available treatments alter symptoms differentially. Few studies address the symptom specificity of this psychoactive brew.AimsWe examined self-reported effects of ayahuasca on the individual symptoms of depression assessed by the 10-item short-form of Center for Epidemiological Studies of Depression (CESD-10).MethodsWe asked over 120 participants to complete a retrospective assessment of CESD-10 symptoms one month before and one month after using ayahuasca.ResultsParticipants indicated that ayahuasca had a larger influence on affective symptoms like hope, depressed mood, and happiness, than cognitive, interpersonal, and somatic symptoms like restless sleep, loneliness, and difficulty focusing.ConclusionsPotential clients might appreciate identifying if different treatments provide more relief for some depressive symptoms than others. We examined retrospective reports of ayahuasca's potential for differential impact. Those eager to alter hope, happiness, and other affective symptoms will likely find ayahuasca more helpful than those who want an intervention for restless sleep, loneliness, or trouble focusing. This symptom specificity parallels the effects of serotonergic antidepressant medications, suggesting that psychedelic-assisted psychotherapy using ayahuasca might have considerable appeal for those who seek comparable relief but would rather not use prescription serotonergic medications. Jumpstarting psychotherapy with the rapid onset of ayahuasca-induced relief also appears to have potential.

Influences of Suvorexant and Mirtazapine on Chronic Pain-related Sleep Disorder in Neuropathic Pain Model Mice

Chronic pain and sleep disorders are independently associated with a reduction in the quality of life. They can be both a cause and consequence of each other; therefore, they should be treated simultaneously. However, optimal treatments for chronic pain-related sleep disorders are not well established. Here, we aimed to investigate the effects of suvorexant, a novel sleep drug, and mirtazapine, a noradrenergic and specific serotonergic antidepressant, on pain-related sleep disorders in a preclinical neuropathic pain mouse model, which was produced by partial sciatic nerve ligation. We calculated the quantity, duration, and depth of sleep by analyzing the electroencephalogram. Voluntary activity was also evaluated by counting the number of wheel rotations with special cages. Daily administration of suvorexant and mirtazapine normalized the reduced rapid eye movement (REM) and non-REM sleep and improved the fragmented sleep, further regaining the depth of sleep at sleep onset in the chronic pain state. Suvorexant decreased voluntary activity, which was prolonged after the end of administration; however, mirtazapine did not decrease it. Both suvorexant and mirtazapine could be potential therapeutic agents for chronic pain-related sleep disorders.

Homicide attempt due to medication induced mania

Bipolar disorders are a group of mental disorders characterized by fluctuations in mood, with depressive symptoms generally dominating the course of disorder. Research on the efficacy of serotonergic antidepressants in bipolar depression is controversial and as a result, treatment of depressive symptoms in bipolar disorder is difficult. A particularly difficult situation arises when bipolar disorder is unrecognized and the depressive state is treated as major depressive disorder with the use of serotonergic antidepressants, which can result in the phenomenon of antidepressant induced mania (AIM). In this report, we present a case of antidepressant induced mania (AIM) with homicidal ideation after initiation of serotonergic antidepressants. Here, we discuss the importance of monitoring for bipolar disorder after prescribing serotonergic antidepressant therapy as well as medico-legal considerations.

Mirtazapine exerts astrocyte-mediated dopaminergic neuroprotection

Mirtazapine, a noradrenergic and specific serotonergic antidepressant (NaSSA), is known to activate serotonin (5-HT) 1A receptor. Our recent study demonstrated that stimulation of astrocytic 5-HT1A receptors promoted astrocyte proliferation and upregulated antioxidative property in astrocytes to protect dopaminergic neurons against oxidative stress. Here, we evaluated the neuroprotective effects of mirtazapine against dopaminergic neurodegeneration in models of Parkinson’s disease (PD). Mirtazapine administration attenuated the loss of dopaminergic neurons in the substantia nigra and increased the expression of the antioxidative molecule metallothionein (MT) in the striatal astrocytes of 6-hydroxydopamine (6-OHDA)-injected parkinsonian mice via 5-HT1A receptors. Mirtazapine protected dopaminergic neurons against 6-OHDA-induced neurotoxicity in mesencephalic neuron and striatal astrocyte cocultures, but not in enriched neuronal cultures. Mirtazapine-treated neuron-conditioned medium (Mir-NCM) induced astrocyte proliferation and upregulated MT expression via 5-HT1A receptors on astrocytes. Furthermore, treatment with medium from Mir-NCM-treated astrocytes protected dopaminergic neurons against 6-OHDA neurotoxicity, and these effects were attenuated by treatment with a MT-1/2-specific antibody or 5-HT1A antagonist. Our study suggests that mirtazapine could be an effective disease-modifying drug for PD and highlights that astrocytic 5-HT1A receptors may be a novel target for the treatment of PD.

SSRIs modulate asymmetric learning from reward and punishment

Human instrumental learning is driven by a history of outcome success and failure. We demonstrate that week-long treatment with a serotonergic antidepressant modulates a valence-dependent asymmetry in learning from reinforcement. In particular, we show that prolonged boosting of central serotonin reduces reward learning, and enhances punishment learning. This treatment induced learning asymmetry can result in lowered positive and enhanced negative expectations. A consequential effect is more rewarding, and less disappointing, experiences and this may, in part, explain the slow temporal evolution of serotonin’s well-established antidepressant effects.

Understanding the Mechanism of Antidepressant-Related Sexual Dysfunction: Inhibition of Tyrosine Hydroxylase in Dopaminergic Neurons after Treatment with Paroxetine but Not with Agomelatine in Male Rats

Antidepressant-related sexual dysfunction is a frequent adverse event caused by serotonergic activation that intensely affects quality of life and adherence in depressed patients. The dopamine system has multiple effects promoting sexual behavior, but no studies have been carried out to confirm dopaminergic changes involved in animal models after antidepressant use. Methods: The sexual behavior-related dopaminergic system in the rat was studied by comparing two different antidepressants and placebo for 28 days. The antidepressants used were paroxetine (a serotonergic antidepressant that causes highly frequent sexual dysfunction in humans) and agomelatine (a non-serotonergic antidepressant without associated sexual dysfunction). The tyrosine hydroxylase immunoreactivity (THI) in the substantia nigra pars compacta, the ventral tegmental area, the zona incerta, and the hypothalamic arcuate nucleus, as well as the dopaminergic projections to the striatum, hippocampus, cortex, and median eminence were analyzed. Results: The THI decreased significantly in the substantia nigra and ventral tegmental area after treatment with paroxetine, and the labeling was reduced drastically in the zona incerta and mediobasal hypothalamus. The immunoreactive axons in the target regions (striatum, cortex, hippocampus, and median eminence) almost disappeared only in the paroxetine-treated rats. Conversely, after treatment with agomelatine, a moderate reduction in immunoreactivity in the substantia nigra was found without appreciable modifications in the ventral tegmental area, zona incerta, and mediobasal hypothalamus. Nevertheless, no sexual or copulatory behavior was observed in any of the experimental or control groups. Conclusion: Paroxetine but not agomelatine was associated with important decreased activity in dopaminergic areas such as the substantia nigra and ventral tegmental areas that could be associated with sexual performance impairment in humans after antidepressant treatment.

Antidepressiva-Einnahme doch nicht mit Autismus-Spektrum-Störung assoziiert?

Sujan AC et al. Associations of Maternal Antidepressant Use During the First Trimester of Pregnancy With Preterm Birth, Small for Gestational Age, Autism Spectrum Disorder, and Attention-Deficit/Hyperactivity Disorder in Offspring. JAMA 2017; 317: 1553–1562 Brown HK et al. Association Between Serotonergic Antidepressant Use During Pregnancy and Autism Spectrum Disorder in Children. JAMA 2017; 317: 1544–1552 Mezzacappa A et al. Risk for Autism Spectrum Disorders According to Period of Prenatal Antidepressant Exposure: A Systematic Review and Meta-analysis. JAMA Pediatr 2017; DOI: 10.1001/jamapediatrics.2017.0124 Kommentar zu den Studien: Oberlander TF, Zwaigenbaum L. Disentangling Maternal Depression and Antidepressant Use During Pregnancy as Risks for Autism in Children. JAMA 2017; 317: 1533–1534 Bei der Depression handelt es sich um eine der häufigsten Komplikationen während der Schwangerschaft, 10% aller Frauen sind davon betroffen. Frühere Untersuchungen legen nahe, dass eine pränatale Einnahme von Antidepressiva mit neurologischen Entwicklungsproblemen bei den Kindern wie der Autismus-Spektrum-Störung einhergeht. 3 Studien sowie 1 Kommentar haben nun diese mögliche Assoziation sowie alternative Hypothesen überprüft.