Antipsychotics-Induced Changes in Synaptic Architecture and Functional Connectivity: Translational Implications for Treatment Response and Resistance
Andrea de Bartolomeis,
Giuseppe De Simone,
Mariateresa Ciccarelli,
Alessia Castiello,
Benedetta Mazza,
Licia Vellucci,
Annarita Barone
Affiliations
Andrea de Bartolomeis
Section of Psychiatry, Laboratory of Translational and Molecular Psychiatry and Unit of Treatment-Resistant Psychosis, Department of Neuroscience, Reproductive Sciences and Odontostomatology, University Medical School of Naples “Federico II”, Via Pansini 5, 80131 Naples, Italy
Giuseppe De Simone
Section of Psychiatry, Laboratory of Translational and Molecular Psychiatry and Unit of Treatment-Resistant Psychosis, Department of Neuroscience, Reproductive Sciences and Odontostomatology, University Medical School of Naples “Federico II”, Via Pansini 5, 80131 Naples, Italy
Mariateresa Ciccarelli
Section of Psychiatry, Laboratory of Translational and Molecular Psychiatry and Unit of Treatment-Resistant Psychosis, Department of Neuroscience, Reproductive Sciences and Odontostomatology, University Medical School of Naples “Federico II”, Via Pansini 5, 80131 Naples, Italy
Alessia Castiello
Section of Psychiatry, Laboratory of Translational and Molecular Psychiatry and Unit of Treatment-Resistant Psychosis, Department of Neuroscience, Reproductive Sciences and Odontostomatology, University Medical School of Naples “Federico II”, Via Pansini 5, 80131 Naples, Italy
Benedetta Mazza
Section of Psychiatry, Laboratory of Translational and Molecular Psychiatry and Unit of Treatment-Resistant Psychosis, Department of Neuroscience, Reproductive Sciences and Odontostomatology, University Medical School of Naples “Federico II”, Via Pansini 5, 80131 Naples, Italy
Licia Vellucci
Section of Psychiatry, Laboratory of Translational and Molecular Psychiatry and Unit of Treatment-Resistant Psychosis, Department of Neuroscience, Reproductive Sciences and Odontostomatology, University Medical School of Naples “Federico II”, Via Pansini 5, 80131 Naples, Italy
Annarita Barone
Section of Psychiatry, Laboratory of Translational and Molecular Psychiatry and Unit of Treatment-Resistant Psychosis, Department of Neuroscience, Reproductive Sciences and Odontostomatology, University Medical School of Naples “Federico II”, Via Pansini 5, 80131 Naples, Italy
Schizophrenia is a severe mental illness characterized by alterations in processes that regulate both synaptic plasticity and functional connectivity between brain regions. Antipsychotics are the cornerstone of schizophrenia pharmacological treatment and, beyond occupying dopamine D2 receptors, can affect multiple molecular targets, pre- and postsynaptic sites, as well as intracellular effectors. Multiple lines of evidence point to the involvement of antipsychotics in sculpting synaptic architecture and remodeling the neuronal functional unit. Furthermore, there is an increasing awareness that antipsychotics with different receptor profiles could yield different interregional patterns of co-activation. In the present systematic review, we explored the fundamental changes that occur under antipsychotics’ administration, the molecular underpinning, and the consequences in both acute and chronic paradigms. In addition, we investigated the relationship between synaptic plasticity and functional connectivity and systematized evidence on different topographical patterns of activation induced by typical and atypical antipsychotics.
