Repeated Ketamine Infusions for Comorbid PTSD and MDD in Veterans

Inclusion Criteria: For the PTSD+MDD group, inclusion criteria are: 1. Female/Male veterans 2. 18 to 75 years old 3. Meets DSM-5 criteria for MDD, single or recurrent, moderate-severe without psychotic features 4. Meets DSM-5 criteria for chronic PTSD or subthreshold PTSD \[meets criterion A (traumatic event), criterion B (intrusion symptoms), and 2 of the following 3 criteria: C (avoidance symptoms), D (negative alterations in cognitions and mood), or E (marked alterations in arousal and reactivity)\] 5. If applicable, 6 weeks of stable antidepressants/augmenting agents 6. Sixth grade reading level 7. Ability to provide consent For the Healthy Controls group, inclusion criteria are: 1. Female/Male veterans 2. 18 to 75 years old 3. Does not meet DSM-5 criteria for MDD, single or recurrent, moderate-severe without psychotic features 4. Does not meet DSM-5 criteria for chronic PTSD or subthreshold PTSD 5. Not on medications for managing a psychiatric indication 6. Sixth grade reading level 7. Ability to provide consent For the Depression-only group, inclusion criteria are: 1. Female/Male veterans 2. 18 to 75 years old 3. Experienced a traumatic event that meets DSM-5 criterion A for a diagnosis of PTSD but does not meet sufficient criteria (B-E) necessary for a diagnosis of PTSD or subthreshold PTSD 4. Meets criteria for MDD, single or recurrent, moderate-severe 5. If applicable, 6 weeks of stable antidepressants/augmenting agents 6. Sixth grade reading level 7. Ability to provide consent For the PTSD-only group, inclusion criteria are: 1. Female/Male veterans 2. 18 to 75 years old 3. Meets DSM-5 criteria for chronic PTSD or subthreshold PTSD \[meets criterion A (traumatic event), criterion B (intrusion symptoms), and 2 of the following 3 criteria: C (avoidance symptoms), D (negative alterations in cognitions and mood), or E (marked alterations in arousal and reactivity)\] 4. Does not meet DSM-5 criteria for MDD, single or recurrent, moderate-severe without psychotic features 5. If applicable, 6 weeks of stable antidepressants/augmenting agents 6. Sixth grade reading level 7. Ability to provide consent Exclusion Criteria: For the PTSD+MDD group, exclusion criteria are: 1. Inability or unwillingness to provide written informed consent 2. Moderate/severe cognitive impairment 3. Current or lifetime diagnosis of psychosis-related disorder, bipolar I or II disorder, substance-induced mood disorder, or any mood disorder due to a general medical condition 4. History of moderate or severe traumatic brain injury 5. History of comorbid substance disorder within 1 month of screening 6. Prior use of ketamine as an antidepressant 7. Clinically unstable medical illness 8. For women: pregnancy (confirmed by baseline lab test), the initiation of female hormonal treatments within 3 months of screening, or inability or unwillingness to use a medically accepted contraceptive method for the duration of the study 9. Imminent risk of suicidal/homicidal ideation and/or behavior 10. Inability to undergo MRI (i.e. claustrophobia, ferromagnetic implants, etc.) For the Healthy Controls group, exclusion criteria are: 1. Inability or unwillingness to provide written informed consent 2. Moderate/severe cognitive impairment 3. History of any major medical or psychiatric disorders 4. Current or lifetime diagnosis of psychosis-related disorder, bipolar I or II disorder, substance-induced mood disorder, or any mood disorder due to a general medical condition 5. History of moderate or severe traumatic brain injury 6. History of comorbid substance disorder within 1 month of screening 7. Prior use of ketamine as an antidepressant 8. Clinically unstable medical illness 9. For women: pregnancy (confirmed by baseline lab test), the initiation of female hormonal treatments within 3 months of screening, or inability or unwillingness to use a medically accepted contraceptive method for the duration of the study 10. Imminent risk of suicidal/homicidal ideation and/or behavior 11. Inability to undergo MRI (i.e. claustrophobia, ferromagnetic implants, etc.) For the Depression-only group, exclusion criteria are: 1. Inability or unwillingness to provide written informed consent 2. Moderate/severe cognitive impairment 3. Meet DSM-5 criteria for PTSD or subthreshold PTSD 4. Current or lifetime diagnosis of psychosis-related disorder, bipolar I or II disorder, substance-induced mood disorder, or any mood disorder due to a general medical condition 5. History of moderate or severe traumatic brain injury 6. History of comorbid substance disorder within 1 month of screening 7. Prior use of ketamine as an antidepressant 8. Clinically unstable medical illness 9. For women: pregnancy (confirmed by baseline lab test), the initiation of female hormonal treatments within 3 months of screening, or inability or unwillingness to use a medically accepted contraceptive method for the duration of the study 10. Imminent risk of suicidal/homicidal ideation and/or behavior 11. Inability to undergo MRI (i.e. claustrophobia, ferromagnetic implants, etc.) For the PTSD-only group, exclusion criteria are: 1. Inability or unwillingness to provide written informed consent 2. Moderate/severe cognitive impairment 3. Meet DSM-5 criteria for a diagnosis of MDD, single or recurrent, moderate to severe 4. Current or lifetime diagnosis of psychosis-related disorder, bipolar I or II disorder, substance-induced mood disorder, or any mood disorder due to a general medical condition 5. History of moderate or severe traumatic brain injury 6. History of comorbid substance disorder within 1 month of screening 7. Prior use of ketamine as an antidepressant 8. Clinically unstable medical illness 9. For women: pregnancy (confirmed by baseline lab test), the initiation of female hormonal treatments within 3 months of screening, or inability or unwillingness to use a medically accepted contraceptive method for the duration of the study 10. Imminent risk of suicidal/homicidal ideation and/or behavior 11. Inability to undergo MRI (i.e. claustrophobia, ferromagnetic implants, etc.)