This multi-center, randomized, double-blind, parallel-group, placebo-controlled study will evaluate the efficacy and safety of RO4917838 in participants with persistent, predominant negative symptoms of schizophrenia. Participants, on stable treatment with antipsychotics, will be randomized to receive daily oral doses of RO4917838 or matching placebo for 56 weeks (treatment period 1 of 24 weeks and treatment period 2 of 32 weeks), followed by an optional treatment extension for up to 3 years. After 52 weeks, participants who were originally randomized to an active treatment will be randomly assigned to receive either placebo or continue on the originally assigned study treatment for 4 weeks washout period (Week 52 to Week 56) for the assessment of potential withdrawal effects in a blinded manner using participants staying on active treatment as a control. Participants initially randomized to placebo will remain on placebo. After 56 weeks, participants who were switched to placebo in the washout period will return to their blinded, active treatment arm.

Inclusion Criteria:

• Diagnosis of schizophrenia of paranoid, disorganized, residual, undifferentiated or catatonic subtype
• Predominant negative symptoms
• With the exception of clozapine, participants are on any of the available marketed atypical or typical antipsychotics (treatment with a maximum of two antipsychotics)

Exclusion Criteria:

• Evidence that participant has clinically significant, uncontrolled and unstable disorder (e.g. cardiovascular, renal, hepatic disorder)
• Body Mass Index (BMI) of less than (<) 17 or greater than (>) 40 kilograms per meter square (kg/m^2)
• Depressive symptoms, defined as a score of 9 or greater on the Calgary Depression Rating Scale for Schizophrenia (CDSS)
• A severity score of 3 or greater on the Parkinsonism item of the Exrapyramidal Symptoms Rating Scale-Abbreviated (ESRS-A) (Clinical Global Impression, Parkinsonism)