Schizophrenia

Clinical picture (children and adolescents)

• Early-onset schizophrenia (before age 18) is rare; onset before age 13 is very rare. Onset is often insidious and may be preceded by social withdrawal and falling school performance. B
• Differential diagnosis: mood disorder with psychotic features, substance use, autism, organic causes. A

Circuits and networks

• Caudate Nucleus and Putamen (especially the associative striatum): dopamine synthesis capacity and release are increased (Howes et al., 2012). A
• Ventral Tegmental Area, Substantia Nigra: dopamine sources; overactivity of the mesolimbic pathway and underactivity of the mesocortical pathway is the classic model. B
• Hippocampus: the largest volume difference in ENIGMA (d = −0.46) (van Erp et al., 2016); hippocampal overactivity is proposed to drive dopamine neurons. B
• Dorsolateral Prefrontal Cortex: working memory and cognitive control; negative and cognitive symptoms. B
• Superior Temporal Gyrus & Wernicke (auditory cortex): auditory hallucinations. B
• Thalamus, Amygdala, Nucleus Accumbens: smaller in ENIGMA; Globus Pallidus (pallidum) larger. A

Neurotransmitter systems

• Dopamine (dopamine): in a meta-analysis of 44 studies, presynaptic dopamine function was increased (d = 0.79); a small increase in D2/3 receptors (d = 0.26) was not seen in unmedicated patients (Howes et al., 2012). A
• Glutamate (NMDA receptor hypofunction hypothesis). B
• The common action of antipsychotics is D2 receptor blockade. A

Imaging and neurobiological findings

• ENIGMA-SZ (2,028 patients, 2,540 controls): smaller hippocampus (d = −0.46), amygdala (−0.31), thalamus (−0.31) and accumbens (−0.25); larger pallidum (+0.21) and lateral ventricles (+0.37) (van Erp et al., 2016). A
• The aberrant salience model: dysregulated dopamine release lends meaning to neutral stimuli; delusions are an attempt to explain this experience (Kapur, 2003). Theoretical. C

Developmental course

• Neurodevelopmental model: risk begins early in life, and symptoms appear in adolescence and young adulthood, coinciding with prefrontal maturation. B

Treatment and the systems it targets

• Antipsychotics (D2 blockade): many second-generation antipsychotics are approved for adolescents; weight and metabolic side effects are monitored. A
• In treatment-resistant early-onset schizophrenia, clozapine is the most effective option: in a double-blind trial of 39 adolescents, response was 66% with clozapine and 33% with olanzapine (Kumra et al., 2008); blood counts must be monitored. B
• Psychosocial: family intervention, psychoeducation, cognitive behavioral therapy, school and work support. A

Link to the book (The Green Walnut on the Couch)

• In the book (translated from the Turkish original):
  • SEEKING system, clinical: "anhedonia, depression, addiction, ADHD, mania, and excessive attribution of meaning in psychosis".
  • Mesolimbic pathway, note: "the indirect or direct target of most drugs used in psychiatry (stimulants, antipsychotics, even some antidepressants)".

In the atlas

Regions

Core structures in bold.

Networks

Neurotransmitter pathways

Panksepp systems

References

1. Howes OD et al. (2012). The nature of dopamine dysfunction in schizophrenia and what this means for treatment: meta-analysis of imaging studies. Archives of General Psychiatry, 69(8), 776–786. Search PubMed
2. Kapur S (2003). Psychosis as a state of aberrant salience. American Journal of Psychiatry, 160(1), 13–23. Search PubMed
3. van Erp TGM et al. (2016). Subcortical brain volume abnormalities in 2028 individuals with schizophrenia and 2540 healthy controls via the ENIGMA consortium. Molecular Psychiatry, 21(4), 547–553. Search PubMed
4. Kumra S et al. (2008). Clozapine and "high-dose" olanzapine in refractory early-onset schizophrenia: a 12-week randomized and double-blind comparison. Biological Psychiatry, 63(5), 524–529. Search PubMed