Post-partum depression (PPD) is a prevalent subtype of major depressive disorder that causes a significant distress to the woman and substantial impact on the whole family. Many studies implicate the glutamatergic system in pathological processes relevant to PPD disorders. There is evidence that cell adhesion molecules (CAMs) play a key role in how glutamatergic circuits wire up during development and how glutamatergic synapses, once formed, operate. However, it is unclear how dysregulation in diverse CAMs alter glutamatergic circuitries responsible for emotional and social behavior.

Here, the investigators propose to evaluate the molecular and neurobiological underpinnings of PPD focusing on CAMs at glutamatergic synapses by using an integrated approach from mouse models to human patients. Moreover, the investigators will also perform a pilot study to investigate the impact of selective antidepressants, known to be linked to CAMs, in both human and mice.

Patients will be recruited by the physician in charge of the study or collaborators of the S.C. Neonatology and Neonatal Intensive Care Unit of the IRCCS Ca' Granda Ospedale Maggiore Policlinico Foundation upon referral from the S.C. Psychiatry of the same institution. In the study, exposure to citalopram treatment will be 12 weeks with follow-up every 4 weeks. At each participant, at the time of enrollment, will be assigned a unique code so that only the local investigators can trace the subject's identity. As part of a scheduled visit to assess the clinical diagnosis, the PPD patient will be offered to participate in the study, after the appropriate signing of informed consent, the verification of absence of criteria for exclusion and existence of the study inclusion criteria. If these criteria are met, some demographic and clinical medical history of the women with PPD will be collected, as already provided by clinical practice for the management of the disease. Patients will undergo MRI scanning at baseline at the S.C. Neuroradiology of the Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico and will begin the pharmacological treatment with citalopram. It is emphasized that the administration of citalopram therapy for the treatment of depressive symptomatology will be proposed and carried out in the patient due to clinical needs, based on the judgment of the competent physician and as would already be the case in practice, thus completely independent of participation or non-participation in the present study. Neuroimaging data will be obtained with a Philips 3T magnetic resonance imaging MRI machine. For each patient enrolled in the study, a structural T1 sequence (3D MPRAGE) is acquired.

T1-weighted MRI images will be used to study the differences brain morphology, including the volumes of gray matter (GM) and white matter (WM) and voxel-based morphometry. In a comparison parallel between regions of interest (ROIs), regional volumes will be estimated using the automated anatomical labeling atlas (AAL) as a reference, with emphasis on the dorsolateral PFC (DL)/ventrolateral (VL), cingulate cortex, amygdala and hippocampus. Further regional analysis will allow estimation, in addition to cortical volumes and subcortical volumes, cortical thickness, cortical surface area, and the cortical gyrification of the Desikan-Killiany atlas regions. During treatment with citalopram, patients will be visited, as per standard clinical practice, every 4 weeks. At each of these follow-up visits will be administered to patients by medical specialists the Brief Psychiatric Rating Scale (BPRS) and the Hamilton Depression Rating Scale (HAM- D) to study symptomatology depression. Patients will be, instead, self-administered in Italian language the Maternal Postnatal Attachment Scale (MPAS) and the Parental Stress Index (PSI) to investigate mother-child attachment and parental stress. The time scheduled for completion of both scales will be about 40 minutes. At 12 weeks, as per practice, the MRI scan will be repeated at the S.C. Neuroradiology Department of the Foundation. The following variables will be collected as part of this study: socio-demographic variables (age, schooling, socio-economic);

• clinical/anamnestic variables (age of onset, duration of untreated treated, drug therapy, comorbidities, familiarity, substance abuse/dependence);
• BPRS and HAM-D scales scores for symptomatology assessment (T0, T1, T2, T3);
• MPAS and PSI scales scores for the assessment of mothers child attachment. (T0, T1, T2, T3);
• MRI scan data (T0, T3): the images will be used to study brain morphological differences, including GM and WM volumes, and voxel-based morphometry. In a parallel comparison between regions of interest (ROI), regional volumes will be estimated using as a reference the automated anatomical labeling atlas (AAL), with particular attention to the dorsolateral (DL)/ventrolateral (VL) PFC, cingulate cortex, amygdala and hippocampus. A further regional analysis will make it possible to estimate, in addition to cortical and subcortical volumes, the thickness cortical, cortical surface area and cortical gyrification of the Desikan-Killiany atlas regions.

Inclusion Criteria:

• Age between 18 and 40 years;
• female gender;
• PPD diagnosed by DSM-5 structured clinical interview support (SCID-5) by trained medical personnel;
• comorbidity with metabolic syndrome, which can lead to brain damage and cognitive flaws;
• need to start citalopram therapy for clinical needs (and therefore independent of study participation) or already on therapy for no more than two weeks;
• moderate to severe depression according to the 17-item HAM-D (score 14-24);
• absence of disabling medical and/or neurological conditions, including heart attacks, brain injuries, neurodegenerative diseases, head trauma with loss of consciousness for more than 30 minutes;
• Absence of concomitant psychiatric therapies (antidepressants, antipsychotics of the first and second generation and mood stabilizers);
• absence of contraindications for MRI scanning;
• patients who have signed informed consent.

Exclusion Criteria:

• age below 18 years or above 40 years;
• diagnosis different from PPD based on SCID-5;
• absence of metabolic syndrome;
• low depression according to the 17-item HAM-D (score less than 14);
• presence of disabling medical and/or neurological conditions, including heart attacks, brain injuries, neurodegenerative diseases, head trauma with loss of consciousness for more than 30 minutes;
• presence of concomitant drug therapies (antidepressants, first- and second-generation antipsychotics and mood stabilizers);
• presence of contraindications for MRI scanning;
• presence of contraindications for citalopram;
• patients who have not signed informed consent.

female

Women, aged 18 years to 40 years of age or older, with PPD who will be enrolled by the S.C. Neonatology and Neonatal Intensive Care Unit of the IRCCS Ca' Granda Ospedale Maggiore Policlinico Foundation upon referral from the S.C. Psychiatry of the same institution.