Do antipsychotics alter functional connectivity of brain? JAMA ps.Jan.2015


Abnormalities in corticostrital connections is  considered to be fundamental pathology in Schizophrenia. Changes in blood flow and  dopamine levels have been repeatedly demonstrated in schizophrenia previously. Functional connectivity studies aim to study activation levels in the key regions. Altered functional connectivity between striatum and cortical regions can be seen as   a risk phenotype in patients with first-episode psychosis (FEP) and their relatives.

What is the effect of antipsychotic medications on the  cortico stratal functional circuitry ? How does it relate to symptom changes?

Deepak K. Sarpal and colleagues from US  examined the relationship between changes in striatal circuitry and reduction in psychotic symptoms after treatment with antipsychotic medication ( risperidone or aripiprazole)  with first episode of Schizophrenia. Patients  ( 15-40 age group) and controls were scanned at baseline. After 12 weeks of antipsychotic treatment ( aripiprazole or risperidone) patients were scanned again and were compared with control scans at 12 weeks. Particiapnts were diagnosed by structured interview, they had less than 2 weeks of cumulative antipsychotic exposure ( life time) prior to entry to the study. BPRS was used to rate symptoms.All patients received double-blind treatment with either risperidone (dose range, 1-6 mg) or aripiprazole (5-30 mg) for 16 week.


With improvement of psychosis researchers  observed a significant increase in functional connectivity between the right dorsal caudate and several pre- frontal regions including the anterior cingulate, right dorsolateral prefrontal cortex, and orbitofrontal cortex. Improvement of psychosis was associated with alterations in functional connections of the striatum. Striatum is often implicated in the pathophysiology of psychosis and is rich in  D2 receptors.

Significantly increased connectivity between striatal regions and the dorsal anterior cingulate implicated a role for error monitoring and cognitive control in recovery from psychotic symptoms.Functional coordination between the striatum and pre frontal and limbic systems may influence salience processing as psychotic symptoms are reduced.

Lui and colleagues 2010 found that  SGAs increased the amplitude of low-frequency fluctuations (ALFF) of blood oxygen level-dependent signals in prefrontal and parietal cortex, left superior temporal cortex, and right caudate nucleus. An association with reduction of clinical symptoms were also noted.Prospective nature of the present study adds greater interest in its observations.


It is important to note that in this study there was no baseline difference between the two groups in functional connectivity. Functional circuits are under more scrutiny and are probably key in understanding how symptoms appear as well as respond to medications.

Summary of the article: 

Antipsychotic treatment and functional connectivity of the striatum in first-episode schizophrenia.

Sarpal DK, Robinson DG, Lencz T, Argyelan M, Ikuta T, Karlsgodt K, Gallego JA, Kane JM, Szeszko PR, Malhotra AK.

JAMA Psychiatry. 2015 Jan 1;72(1):5-13

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