**2. Overview of SCZ**

#### **2.1 Clinical presentation**

The word SCZ originated by Eugen Bleuler in 1908, is derived from the Greek words 'schizo' (splitting) and 'phren' (mind) and defines a functional psychotic illness typified by the occurrence of hallucinations, delusional opinions, and disruptions of perception, thought, and behavior. Conventionally, symptoms have been separated into two major classifications: positive symptoms that comprise delusions, hallucinations, and formal thought disorders, and negative symptoms such as poverty of speech, anhedonia, and lack of motivation. SCZ diagnosis is clinical, solely done after acquiring a detailed psychiatric record and excluding further reasons for psychosis. Risk factors comprise the season of birth, severe maternal malnutrition, maternal influenza in pregnancy, family history, childhood trauma, social isolation, cannabis use, minority ethnicity, complications of giving birth, and urbanization [23–25].

SCZ is a developmental disorder and it is now widely accepted that astrocytes play an important role during both pre and postnatal development and continue their important role in development into adulthood by regulating establishment of neuronal circuits [26] and by regulating multiple homeostatic functions, such as buffering extracellular potassium or modulation of synaptic activity [27] and functional hyperemia [28], respectively. They offer metabolic support for synaptic activity and are also required for creating and maintaining synapses [29]. Changes in astrocytic numbers have been demonstrated to cause cognitive impairment, which is consistent with the essential roles of astrocytes in neural circuit functioning. In the astrocyte-specific toxin L-aminoadipate (L-AA) model [30] or in a transgenic mouse line with inducible and selective tetanus neurotoxin (TeNT) expression in astrocytes [31], mice exhibited deficits in set-shifting attention, working memory, reversal learning [30], recognition memory, and abnormal cortical gamma oscillations [31]. Similarly, decreased expression of the astrocytic glutamate transporter GLT-1 lowered prepulse suppression of the acoustic startle response [32], which is a well-established characteristic of SCZ. Changes in astrocytic cell density and morphology in the mouse prefrontal cortex (PFC) cause cognitive dysfunctions associated with the subcortical zone (SCZ) [30, 31].
