This is a retrospective observational study to evaluate the clinical utility of blood-based biomarkers in the diagnosis and management of patients with a neurodegenerative disease (ND) or mental disorder (MD).

This study will collect clinical and biomarker data from patients and controls to identify a) a blood-based diagnostic biomarker for mental disorders, and b) a blood-based biomarker that could be used as a surrogate end-point for the principal neuropsychiatric symptoms.

Specific research questions are:

Can blood-based biomarkers provide a faster more objective diagnosis for major depressive disorder, bipolar disorders or schizophrenia? Can the same biomarkers also aid in the differential diagnosis from neurodegenerative diseases? Do blood-based synaptic biomarkers correlate with structural and functional brain changes, cognitive performance and psychiatric symptoms in patients with major depressive disorder, bipolar disorders, schizophrenia, Alzheimer's disease, dementia with Lewy bodies, frontotemporal dementia or Parkinson's disease? Can the blood-based synaptic biomarkers predict therapeutic response in patients with major depressive disorder, bipolar disorders or schizophrenia?

Inclusion Criteria:

• Age>18 and donation of blood,
• full clinical and psychological assessment
• Available neuroimaging is optional as not all patients are suitable.
• Age and sex-matched unaffected volunteers without a MD or ND diagnosis are used as controls.
• Unaffected controls are usually spouses or children of patients that are informed about our studies at each clinical site.

Exclusion Criteria:

• Lack of neuropsychological data,
• anticoagulant treatment such as acenocoumarol, heparin, warfarin, dabigatran, rivaroxaban, apixaban, drug abuse in the last year,
• medical history of cancer affecting the central nervous system that has not been in complete remission for 5 years or longer,
• the patient has received potentially neurotoxic chemotherapy and/or patient has received cranial radiotherapy.
• Clinical diagnosis of Alzheimer's disease where pathophysiological markers (measured in CSF or plasma) are inconsistent with Alzheimer's disease pathophysiology.
• Cognitively healthy volunteers where pathophysiological markers (measured in CSF or plasma) are consistent with Alzheimer's disease or other neurodegenerative pathophysiology.

Patients will be recruited from specialized clinics at Barcelona (Spain), Perugia (Italy), Ulm (Germany), Halle (Germany) and Kuopio (Finland). Target % female in schizophrenia (30%), major depressive disorder (50%), bipolar disorder and controls (55%), Alzheimer's disease and controls (60%), frontotemporal dementia (65%), controls (65%). These percentages match those typically found in these disorders. Unaffected controls are usually spouses or children of patients that are informed about our studies at each clinical site.