Attenuation of auditory mismatch negativity in serotonin transporter knockout mice with anxiety-related behaviors

Pan, Wenlu; Lyu, Kexin; Zhang, Hongzheng; Li, Cuixian; Chen, Peng; Ying, Ming; Chen, Fangyi; Tang, Jie

doi:10.1016/j.bbr.2019.112387

Cited by 14 publications

(9 citation statements)

References 53 publications

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“…Second, the patients with MDD and BD were taking medications at the time of testing. Although neither typical nor atypical antipsychotics appear to affect MMN amplitudes in patients with schizophrenia 52,78 , the benzodiazepine and antidepressants which are frequently used in patients with mood disorders have been known to affect MMN amplitudes in previous studies [79][80][81] . Therefore, a further study controlling for these medication effects will be needed.…”

Section: Discussionmentioning

confidence: 99%

Mismatch negativity indices and functional outcomes in unipolar and bipolar depression

Kim

Baek

Shim

et al. 2020

Sci Rep

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the aim of the study was to explore the association between functional outcomes and mismatch negativity (MMN) activity in participants with mood disorders. The study participants were 27 subjects with major depressive disorder (MDD), 29 subjects with bipolar disorder (BD), and 33 healthy controls who performed a passive auditory oddball paradigm while electroencephalography (eeG) was recorded. peak amplitudes and source activity of the MMn were compared across groups. Mood and anxiety symptoms were evaluated. the functional levels were the lowest in the BD group, followed by the MDD and healthy control groups. The subjects with BD had significantly lower MMN amplitudes at the frontal and frontocentral electrodes than the healthy controls. the source activity of the MMn from the left anterior cingulate cortex, inferior frontal gyrus, and middle frontal gyrus was significantly increased in the BD group compared to the MDD group. Significant correlations were detected between the functional outcomes and MMn amplitudes at frontal and frontocentral sites. The functional outcome was significantly correlated with left frontal regions. In conclusion, MMN activity appears to be a promising candidate as an evaluation tool for functional outcomes in mood disorders. Bipolar disorder (BD) and major depressive disorder (MDD) are chronic, severe and recurrent mood disorders with substantial disease burden 1. As these two psychiatric conditions both involve severe depressive symptoms, misdiagnosis of BD as unipolar depression is a serious clinical problem 2. Previous studies suggested that C-reactive protein level 3 and heart rate variability 4 are candidate biomarkers for discriminating between bipolar depression and unipolar depression. In addition, electroencephalography (EEG) cordance and coherence values may potentially discriminate unipolar from bipolar depression 5. Although it is important to find biomarkers to enable the differential diagnosis between unipolar and bipolar depression, relatively few studies have addressed this. As such, promising biomarkers to differentiate between the two conditions are needed. Many patients with BD or MDD usually experience serious functional decline 6. Depressive symptoms have been shown to be associated with functional role impairments in multiple domains, such as duties at work or school, responsibilities at home, and relationships with family and friends 7. A previous study found that only 38% patients with major mood disorder achieved functional recovery within 2 years 8. The psychosocial disability resulting from depression is extensive, and encompasses multiple domains, including work and social interactions, independent living in the community, family adjustment, mortality, and quality of life 6. However, it remains unclear why functional decline is so pervasive in mood disorders. In addition, very few studies have assessed the specific biomarkers related to functional decline. Psychosocial functioning is defined as a person's capability to conduct daily life tasks and to engag...

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Section: Discussionmentioning

confidence: 99%

Mismatch negativity indices and functional outcomes in unipolar and bipolar depression

Kim

Baek

Shim

et al. 2020

Sci Rep

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“…Similarly, manipulations of rodent brain serotonin levels during early development, through either increases (produced in SERT or monoamine oxidase KO mice) or decreases (produced by parachlorophenylalanine or other treatments), alter the formation of the whisker (barrel) representation in the primary somatosensory cortex and promote aggressive and/or anxiety-related behaviors (Cases et al, 1995(Cases et al, , 1996Persico et al, 2000;Persico et al, 2001;Holmes et al, 2003;Jennings et al, 2006). In our previous study, auditory mismatch negativity response was found abolished by SERT KO, indicating the low ability in frequency discrimination (Pan et al, 2020). This finding was supported by the functional changes of AC observed in the present study.…”

Section: Discussionmentioning

confidence: 84%

“…This finding was supported by the functional changes of AC observed in the present study. Under the administration of SSRIs, the animal showed anxiety-related and ASD-like behavior (Simpson et al, 2011;Pan et al, 2020). Although the abnormal behavior and auditory function were quite consistent in SERT KO and SSRI-administered animals, the direct evidence is still very limited for us to understand the effects of SSRIs on development and function of cortical circuits.…”

Section: Discussionmentioning

confidence: 99%

“…008,355) and backcrossed with C57BL/6J background mice (Bengel et al, 1998). Polymerase chain reaction (PCR) protocol used for genotyping SERT KO mice has been reported in our previous literature (Pan et al, 2020). Male and female mice aged 2-4 months and weighting 20-26 g were employed in our test.…”

Section: Subjectsmentioning

confidence: 99%

“…Pre-and post-natal exposure to the SSRI disturbed the chemoarchitecture of the mouse auditory cortex (AC) and resulted in ASD-like behavior (Simpson et al, 2011). Our previous study found that both SSRI treatment and SERT knockout (KO) did not change the auditory brain responses but abolished the auditory mismatch negativity in adult animals (Pan et al, 2020). These investigations suggest that SERT may affect the auditory functions by manipulating the serotonin level and serotonergic neurons of AC.…”

Section: Introductionmentioning

confidence: 96%

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Serotonin Transporter Defect Disturbs Structure and Function of the Auditory Cortex in Mice

Pan

Zhao

et al. 2021

Front. Neurosci.

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Serotonin transporter (SERT) modulates the level of 5-HT and significantly affects the activity of serotonergic neurons in the central nervous system. The manipulation of SERT has lasting neurobiological and behavioral consequences, including developmental dysfunction, depression, and anxiety. Auditory disorders have been widely reported as the adverse events of these mental diseases. It is unclear how SERT impacts neuronal connections/interactions and what mechanism(s) may elicit the disruption of normal neural network functions in auditory cortex. In the present study, we report on the neuronal morphology and function of auditory cortex in SERT knockout (KO) mice. We show that the dendritic length of the fourth layer (L-IV) pyramidal neurons and the second-to-third layer (L-II/III) interneurons were reduced in the auditory cortex of the SERT KO mice. The number and density of dendritic spines of these neurons were significantly less than those of wild-type neurons. Also, the frequency-tonotopic organization of primary auditory cortex was disrupted in SERT KO mice. The auditory neurons of SERT KO mice exhibited border frequency tuning with high-intensity thresholds. These findings indicate that SERT plays a key role in development and functional maintenance of auditory cortical neurons. Auditory function should be examined when SERT is selected as a target in the treatment for psychiatric disorders.

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The effect of SSRIs on unconditioned anxiety: a systematic review and meta-analysis of animal studies

Heesbeen,

van Kampen,

Verdouw

et al. 2024

Psychopharmacology

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Rationale Selective serotonin reuptake inhibitors (SSRIs) are the first choice of treatment for anxiety-like disorders. However, which aspects of anxiety are affected by SSRIs is not yet fully understood. Objective We aimed to systematically review the effect of six clinically effective SSRIs on four aspects of unconditioned anxiety: approach-avoidance behaviour (elevated plus maze), repetitive behaviour (marble burying), distress behaviour (ultrasonic vocalization), and activation of the autonomous nervous system (stress-induced hyperthermia). Methods We identified publications by searching Medline and Embase databases and assessed the risk of bias. A random effects meta-analysis was performed and moderator effects were analysed with Bayesian penalized meta-regression. Results Our search yielded 105 elevated plus maze, 63 marble burying, 11 ultrasonic vocalization, and 7 stress-induced hyperthermia articles. Meta-analysis suggested that SSRIs reduce anxiety-like behaviour in the elevated plus maze, marble burying and ultrasonic vocalization test and that effects are moderated by pre-existing stress conditions (elevated plus maze) and dose dependency (marble burying) but not by duration of treatment or type of SSRI. The reporting quality was low, publication bias was likely, and heterogeneity was high. Conclusion SSRIs seem to reduce a broad range of unconditioned anxiety-associated behaviours. These results should be interpreted with caution due to a high risk of bias, likely occurrence of publication bias, substantial heterogeneity and limited moderator data availability. Our review demonstrates the importance of including bias assessments when interpreting meta-analysis results. We further recommend improving the reporting quality, the conduct of animal research, and the publication of all results regardless of significance.

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Attenuation of auditory mismatch negativity in serotonin transporter knockout mice with anxiety-related behaviors

Cited by 14 publications

References 53 publications

Mismatch negativity indices and functional outcomes in unipolar and bipolar depression

Mismatch negativity indices and functional outcomes in unipolar and bipolar depression

Serotonin Transporter Defect Disturbs Structure and Function of the Auditory Cortex in Mice

The effect of SSRIs on unconditioned anxiety: a systematic review and meta-analysis of animal studies

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