Adolescent Psychotic Disorders. REPLY 1

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 A polygenic risk score is a simplified measure of genetic risk and consists of a total of all high-risk genes for schizophrenia an individual possesses (Keshavan et al., 2020; Stahl, 2021). The neurodevelopmental hypothesis of schizophrenia which posits that high-risk gens are responsible for aberrant synaptogenesis and later, competitive neuronal elimination, explains why symptoms of schizophrenia are often unmasked in adolescence (Stahl, 2021).

Yet if genetics were the only risk factor for schizophrenia, we would see the illness occurring in all sets of identical twins.  However, the risk for schizophrenia among an identical twin whose twin sibling has the illness is only 48%, which suggests that even when genes are completely shared, environmental factors play a significant role (Keshavan et al., 2020).  Known environmental risk factors for schizophrenia include the following

        Maternal infections exposure to influenza in first half of pregnancy possibly associated with 3x risk for SZ.  Also, higher risk conferred by maternal rubella, toxoplasmosis, HSV type 2

        Obstetric complications Increased risk with complications causing infant hypoxia. emergency caesarian has largest effect size of several associated complications.

        Seasonality of birth One of the most replicated findings. Excess of SZ in winter births.

        Postnatal infections elevated risk with serious infections necessitating hospitalization.

        Substance use- cannabis in particular. Interacts with COMT and AKT1 high risk genes.

        Maternal nutrition/malnutrition Increased rates of SZ replicated in 3 famine studies.

         Autoimmune disorders Higher incidence interfaced with type 1 diabetes, celiac disease, autoimmune thyroid disease and SLE. One mechanism suggested involves inflammation.

        Childhood trauma- Evidence is not yet robust. Studies investigating relationship done with small sample sizes. Need more studies.

        Urban birth- risk association consistently replicated

        Social Status- Decreased social status confers more risk.

        Stress Repeated and severe stress. Prenatal risk has strong association.

        Minority Status- Increased risk for ethnic minorities.

        Immigration Status Elevated risk seen for 1st and even 2nd generation immigrants.

        Inadequate social support- increases risk for SZ visa vie increased stress.

        Advanced paternal age Increasing risk with advancing paternal age. One of most replicated associations with SZ risk. Fathers age 45 -49 : 2x risk; Fathers age 50 yrs and older 3 x risk than offspring of fathers 25 and younger.

(Keshavan et al., 2020) 

Not all adolescents showing symptoms of a schizophrenic-type prodromal syndrome will convert to full-blown schizophrenia, however approximately 75% to 80% of persons with schizophrenia experienced a prodrome characterized by negative symptoms of schizophrenia and milder, psychotic-like symptoms before the onset of overt psychosis (Perkins & Lieberman, 2020; Stahl, 2021).  Early intervention during the adolescent years in individuals showing symptoms of the prodromal phase of schizophrenia can alter the likelihood of conversion to psychosis in a person experiencing attenuated psychosis symptoms (Perkins & Lieberman, 2020, p. 14). Psychotherapy reduces the risk of continuing psychosis by roughly 50%. Interestingly, antipsychotics have had a less robust response in this population and thus, they are not considered first line treatment for adolescents in the prodromal phase of the illness (Perkins & Lieberman, 2020). In contrast, pharmacological agents which target glutamate receptors look encouraging (Perkins & Lieberman, 2020). By monitoring symptoms of those adolescents in the early or prodromal stages of the disease, appropriate treatment, can be initiated to either alter the course of the illness, or support the individual moving forward with a diagnosis of schizophrenia.

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