Background and Aims: The costs associated with posttraumatic stress disorder (PTSD) are substantial; PTSD impacts work productivity, relationship functioning, and physical health, with estimated annual costs to VA in disability payments of $4.28 billion. Ineffective treatments substantially contribute to the perpetuation of chronic PTSD symptoms and functional impairment in Veterans and, as a consequence, the enormous public health burden associated with PTSD. Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed class of medications for patients with PTSD. However, many patients are not responsive to SSRIs and there is no rapid, uncomplicated way to determine who will or will not benefit from this family of medications. A pre-medication assessment using auditory event-related potentials (ERPs) offers a possible means for predicting treatment response to SSRIs. More specifically, Loudness Dependence of Auditory Evoked Potentials (LDAEP), derived from responses to a series of increasingly loud tones, appears to be strongly influenced by brain serotonin level and thereby holds considerable promise as an indicator of the brain’s potential responsiveness to SSRIs. The primary aim of the proposed project is to investigate the usefulness of LDAEP for predicting those individuals who will most likely show a favorable or adverse response to SSRIs. A secondary aim is to determine LDAEP cut-off values that would enable a clinician to make an individualized SSRI treatment decision based on a patient’s LDAEP score. A tertiary aim is to evaluate LDAEP as an objective outcome measure of SSRI response. An exploratory aim will test whether the relationships between LDAEP and SSRI response differ for men and women and whether men and women have different optimal LDAEP cut off scores. Study Design: A sample of 94 Veterans with PTSD (50% male; 50% female) will participate in a 12-week sertraline trial preceded by a 4-week single-blinded placebo lead-in phase. Embedded in this study are four assessment sessions: pre-placebo, pre-sertraline, and one and three months after initiating sertraline. The procedures conducted during each assessment session will be mostly the same. Participants will: a) engage in the ERP procedure that will yield the LDAEP score, b) complete a battery of symptom outcome measures including measures of PTSD and depressive symptom severity, c) complete self-report assessments of current medication use, medication adherence, and side effects, and d) provide a blood sample for measurement of SSRI level and platelet measurement of serotonin reuptake. Clinical Implications: Findings from this study may contribute to development of a precision-medicine approach when choosing an initial psychopharmacological intervention for Veterans with PTSD. Development of a biological screening method that can be used to identify those individuals who are most likely to be clinically responsive to an SSRI and those who are more likely t...