They have little effect on negative and cognitive symptoms, which may be helped by additional psychotherapies and medications. There is no single antipsychotic suitable for first-line treatment for everyone, as responses and tolerances vary between people. Stopping medication may be considered after a single psychotic episode where there has been a full recovery with no symptoms for twelve months. Repeated relapses worsen the long-term outlook and the risk of relapse following a second episode is high, and long-term treatment is usually recommended.About half of those with schizophrenia will respond favourably to antipsychotics, and have a good return of functioning. However, positive symptoms persist in up to a third of people. Following two trials of different antipsychotics over six weeks, that also prove ineffective, they will be classed as having treatment resistant schizophrenia (TRS), and clozapine will be offered. Clozapine is of benefit to around half of this group although it has the potentially serious side effect of agranulocytosis (lowered white blood cell count) in less than 4% of people.About 30 to 50 percent of people with schizophrenia do not accept that they have an illness or comply with their recommended treatment. For those who are unwilling or unable to take medication regularly, long-acting injections of antipsychotics may be used, which reduce the risk of relapse to a greater degree than oral medications. When used in combination with psychosocial interventions, they may improve long-term adherence to treatment. Adverse effects
Extrapyramidal symptoms, including akathisia, are associated with all commercially available antipsychotic to varying degrees.
Response to stress can cause lasting changes in the function of the HPA axis possibly disrupting the negative feedback mechanism, homeostasis, and the regulation of emotion leading to altered behaviors.The question of how schizophrenia could be primarily genetically influenced, given that people with schizophrenia have lower fertility rates, is a paradox. It is expected that genetic variants that increase the risk of schizophrenia would be selected against due to their negative effects on reproductive fitness. A number of potential explanations have been proposed, including that alleles associated with schizophrenia risk confers a fitness advantage in unaffected individuals. While some evidence has not supported this idea, others propose that a large number of alleles each contributing a small amount can persist.A meta-analysis found that oxidative DNA damage was significantly increased in schizophrenia. Environmental
Environmental factors, each associated with a slight risk of developing schizophrenia in later life include oxygen deprivation, infection, prenatal maternal stress, and malnutrition in the mother during prenatal development. A risk is associated with maternal obesity, in increasing oxidative stress, and dysregulating the dopamine and serotonin pathways. Both maternal stress and infection have been demonstrated to alter fetal neurodevelopment through an increase of pro-inflammatory cytokines. There is a slighter risk associated with being born in the winter or spring possibly due to vitamin D deficiency or a prenatal viral infection. Other infections during pregnancy or around the time of birth that have been linked to an increased risk include infections by Toxoplasma gondii and Chlamydia. The increased risk is about five to eight percent.