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Bioinformatics of the Brain

this disease. While the studies are generally based on comparisons between

schizophrenia patients and healthy control groups, a significant portion of

them were conducted in patients using medication [73].

Proteomic and phosphoproteomic analyses specific to different regions of

the brain such as the cerebellum, caudate nucleus, posterior cingulate cor-

tex, orbitofrontal cortex, primary auditory cortex, and corpus callosum ob-

tained from schizophrenia patients and controls have pointed out the irreg-

ularity of proteins in oligodendrocytes, astrocytes, glial cells, and synapses.

These were studies that particularly highlighted mitochondrial and synap-

tic proteins. Important proteins involved in cell signaling pathways include

ATP synthase subunit alpha (ATP5A1), postsynaptic density protein 95

(PSD95), calcium/calmodulin-dependent protein kinase II, ephrin B, ciliary

neurotrophic proteins, glutamate, and gamma aminobutyric acid (GABA) re-

ceptors [74–77].

Several recent reports have also examined patients diagnosed with

schizophrenia and bipolar disorder. In these studies, using serum and plasma

samples, irregularities in complement system proteins and lipid proteins were

reported. Interesting findings include changing expressions of complement C9

(C9) and Interleukin 1 Receptor Accessory Protein (IL1RAP), Ankyrin Re-

peat Domain-Containing Protein 12 (ANKRD12), Cadherin 5 (CADH5) in

serum and apolipoproteins in plasma [78–81]. Additionally, a meta-analysis

also revealed downregulation of apolipoproteins [73].

Another focus of proteomic studies in schizophrenia patients has been to

investigate post-treatment drug effects reflected in the serum and plasma

proteome [82]. Proteomic analysis of plasma samples from patients with

schizophrenia revealed that proteins that change in response to treatment are

mostly associated with the immune and inflammatory systems [83]. Although

antipsychotics are the primary treatment drugs for schizophrenia, these drugs

may also have various side effects, especially on fat tissue metabolism. Pro-

teomic examination of olanzapine, risperidone, and haloperidol drug treat-

ments in rats prenatally exposed to MAM (methylazoxymethanol) provided

important information about the adipose tissue proteome and demonstrated

downregulation of proteins belonging to the TOR signaling pathway [84].

Additionally, studies conducted in post-mortem brain tissue samples and

schizophrenia cell models have shown that antipsychotic drugs may have ef-

fects on two post-translational modifications: succinylation and malonylation

[85].

An interesting proteomic study performed on dried blood spots of newborn

babies investigated biomarkers that indicate disease susceptibility. Increased

expression of Alpha-2-antiplasmin (A2AP), Complement C4-A (CO4A) and

Antithrombin-III (ANT3) has been reported [86]. These results may constitute

important data sources for proteomic studies with untreated schizophrenia

patients.