Characterization of the serotonin transporter in lymphocytes and platelets of schizophrenia patients treated with atypical or typical antipsychotics compared to healthy individuals

Barkan, Tamar; Peled, Alva; Modai, Ilan; Weizman, Abraham; Rehavi, Moshe

doi:10.1016/j.euroneuro.2005.11.008

Cited by 13 publications

(5 citation statements)

References 38 publications

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“…We here revealed a potential role of 5-HTT in cognitive deficits via the networks involved in socio-affective processes, resonating with the proposed implication of 5-HTT in the affective domain (87,88). While atypical anti-psychotics including olanzapine and risperidone target also the 5-HT2a serotonin receptor (89,90), their effects on 5-HTT seems to be equivocal (91,92).…”

Section: Molecular Architecture Of the Network Robustly Predicted Cosupporting

confidence: 77%

Intrinsic Connectivity Patterns of Task-Defined Brain Networks Allow Individual Prediction of Cognitive Symptom Dimension of Schizophrenia and Are Linked to Molecular Architecture

Chen

Müller

Dukart

et al. 2021

Biological Psychiatry

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Section: Molecular Architecture Of the Network Robustly Predicted Cosupporting

confidence: 77%

Intrinsic Connectivity Patterns of Task-Defined Brain Networks Allow Individual Prediction of Cognitive Symptom Dimension of Schizophrenia and Are Linked to Molecular Architecture

Chen

Müller

Dukart

et al. 2021

Biological Psychiatry

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“…We here revealed a potential role of 5-HTT in cognitive deficits via the networks involved in socio-affective processes, resonating with the proposed implication of 5-HTT in the affective domain (87,88). While atypical anti-psychotics including olanzapine and risperidone target also the 5-HT 2a serotonin receptor (89,90), their effects on 5-HTT seems to be equivocal (91,92).…”

Section: Molecular Architecture Of the Identified Network Which Robusupporting

confidence: 77%

Connectivity patterns of task-specific brain networks allow individual prediction of cognitive symptom dimension of schizophrenia and link to molecular architecture

Chen

Mueller

Dukart

et al. 2020

Preprint

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AbstractBackgroundDespite the marked inter-individual variability in the clinical presentation of schizophrenia, it remains unclear the extent to which individual dimensions of psychopathology may be reflected in variability across the collective set of functional brain connections. Here, we address this question using network-based predictive modeling of individual psychopathology along four data-driven symptom dimensions. Follow-up analyses assess the molecular underpinnings of predictive networks by relating them to neurotransmitter-receptor distribution patterns.MethodsWe investigated resting-state fMRI data from 147 schizophrenia patients recruited at seven sites. Individual expression along negative, positive, affective, and cognitive symptom dimensions was predicted using relevance vector machine based on functional connectivity within 17 meta-analytic task-networks following a repeated 10-fold cross-validation and leave-one-site-out analyses. Results were validated in an independent sample. Networks robustly predicting individual symptom dimensions were spatially correlated with density maps of nine receptors/transporters from prior molecular imaging in healthy populations.ResultsTen-fold and leave-one-site-out analyses revealed five predictive network-symptom associations. Connectivity within theory-of-mind, cognitive reappraisal, and mirror neuron networks predicted negative, positive, and affective symptom dimensions, respectively. Cognitive dimension was predicted by theory-of-mind and socio-affective-default networks. Importantly, these predictions generalized to the independent sample. Intriguingly, these two networks were positively associated with D1 dopamine receptor and serotonin reuptake transporter densities as well as dopamine-synthesis-capacity.ConclusionsWe revealed a robust association between intrinsic functional connectivity within networks for socio-affective processes and the cognitive dimension of psychopathology. By investigating the molecular architecture, the present work links dopaminergic and serotonergic systems with the functional topography of brain networks underlying cognitive symptoms in schizophrenia.

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“…Clinically, chronic treatment (i.e. >3 weeks) with selective serotonin reuptake inhibitors (SSRIs) has been shown to reduce aggressive outbursts and violent behavior in psychiatric patients (Barkan et al 2006; Blader 2006; Bond 2005; Coccaro and Kavoussi 1997; New et al 2004; Reist et al 2003; Walsh and Dinan 2001). However, SSRIs have occasionally been reported to increase the incidence of aggressive and suicidal behavior, and the causes of these paradoxical effects remain unknown (Spigset 1999; Troisi et al 1995).…”

Section: Serotonin Transporter (5-htt)mentioning

confidence: 99%

Behavioral and Pharmacogenetics of Aggressive Behavior

Takahashi

Quadros

Almeida

et al. 2011

Current Topics in Behavioral Neurosciences

100

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Serotonin (5-HT) has long been considered as a key transmitter in the neurocircuitry controlling aggression. Impaired regulation of each subtype of 5-HT receptor, 5-HT transporter, synthetic and metabolic enzymes has been linked particularly to impulsive aggression. The current summary focuses mostly on recent findings from pharmacological and genetic studies. The pharmacological treatments and genetic manipulations or polymorphisms of a specific target (e.g., 5-HT1A receptor) can often result in inconsistent results on aggression, due to “phasic” effects of pharmacological agents vs “trait”-like effects of genetic manipulations. Also, the local administration of a drug using the intracranial microinjection technique has shown that activation of specific subtypes of 5-HT receptors (5-HT1A and 5-HT1B) in mesocorticolimbic areas can reduce species-typical and other aggressive behaviors, but the same receptors in the medial prefrontal cortex or septal area promote escalated forms of aggression. Thus, there are receptor populations in specific brain regions that preferentially modulate specific types of aggression. Genetic studies have shown important gene × environment interactions; it is likely that the polymorphisms in the genes of 5-HT transporters (e.g., MAO A) or rate-limiting synthetic and metabolic enzymes of 5-HT determine the vulnerability to adverse environmental factors that escalate aggression. We also discuss the interaction between the 5-HT system and other systems. Modulation of 5-HT neurons in the dorsal raphe nucleus by GABA, glutamate, and CRF profoundly regulate aggressive behaviors. Also, interactions of the 5-HT system with other neuropeptides (arginine vasopressin, oxytocin, neuropeptide Y, opioid) have emerged as important neurobiological determinants of aggression. Studies of aggression in genetically modified mice identified several molecules that affect the 5-HT system directly (e.g., Tph2, 5-HT1B, 5-HT transporter, Pet1, MAOA) or indirectly (e.g. BDNF, nNOS, αCaMKII, Neuropeptide Y). The future agenda delineates specific receptor subpopulations for GABA, glutamate and neuropeptides as they modulate the canonical aminergic neurotransmitters in brainstem, limbic and cortical regions with the ultimate outcome of attenuating or escalating aggressive behavior.

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Characterization of the serotonin transporter in lymphocytes and platelets of schizophrenia patients treated with atypical or typical antipsychotics compared to healthy individuals

Cited by 13 publications

References 38 publications

Intrinsic Connectivity Patterns of Task-Defined Brain Networks Allow Individual Prediction of Cognitive Symptom Dimension of Schizophrenia and Are Linked to Molecular Architecture

Intrinsic Connectivity Patterns of Task-Defined Brain Networks Allow Individual Prediction of Cognitive Symptom Dimension of Schizophrenia and Are Linked to Molecular Architecture

Connectivity patterns of task-specific brain networks allow individual prediction of cognitive symptom dimension of schizophrenia and link to molecular architecture

Behavioral and Pharmacogenetics of Aggressive Behavior

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