Back to results

Biomarkers of Conversion Risk and Treatment Response in Early-Stage Schizophrenia

Primary Purpose

Schizophrenia Spectrum and Other Psychotic Disorders

Status

Completed

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

Risperidone

About this trial

This is an interventional basic science trial for Schizophrenia Spectrum and Other Psychotic Disorders

Eligibility Criteria

18 Years - 35 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria (Patients):

Male or females between the ages of 18-35
less than five years (<60 months) of active Diagnostic and Statistical Manual of Mental Disorders (DSM) diagnosis of schizophrenia, schizophreniform, or schizoaffective disorder
Capacity to provide informed consent
No major medical or neurological illness
Medication free (3 weeks without antipsychotic medications)

Exclusion Criteria (Patients):

Current alcohol or drug abuse (<1 month) or substance dependence (<6 months) or substances used within one day of the imaging study.
Pregnant or lactating women or women of child-bearing potential, who are either not surgically-sterile or, for outpatients, not using appropriate methods of birth control.
Intelligence Quotient (IQ) <70
Acute risk for suicide or violence
Presence of pacemaker or any metallic objects in the body that would interfere with the MRS or cause MRI safety problems
Claustrophobia
Any organic brain disorder (including epilepsy, mental retardation, or a medical condition whose pathology or treatment would likely alter the presentation or treatment of SZ
Individuals on anti-epileptic medications (e.g., valproate, carbamazepine) that may affect GABA or Glu
Unstable medical or neurological condition
DSM-V diagnosis of bipolar disorder I
DSM-V diagnosis of major depression with psychotic features
History of non-response to or non-tolerance of Risperidone

Inclusion Criteria (Healthy Controls)

Male or females between the ages of 18-35
less than five years (<60 months) of active DSM diagnosis of schizophrenia, schizophreniform, or schizoaffective disorder
No major medical or neurological illness

Exclusion Criteria (Healthy Controls)

Current alcohol or drug abuse (<1 month) or substance dependence (<6 months) or substances used within one day of the imaging study.
Pregnant or lactating women or women of child-bearing potential, who are either not surgically-sterile or, for outpatients, not using appropriate methods of birth control.
IQ<70
Acute risk for suicide or violence
Presence of pacemaker or any metallic objects in the body that would interfere with the MRS or cause MRI safety problems
Claustrophobia
History of psychotropic medication use such as antipsychotics or antidepressants
Any first-degree family history of psychotic illness
Personal history of any DSM Axis I disorder
Individuals on anti-epileptic medications (e.g., valproate, carbamazepine) that may affect GABA or Glu
Unstable medical or neurological condition
Any organic brain disorder (including epilepsy, mental retardation, or a medical condition whose pathology or treatment would likely alter the presentation or treatment of SZ

Sites / Locations

New York State Psychiatric Institute & Columbia University

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Patient

Control

Arm Description

Medication-free individuals during first-episode of psychosis who will receive 4 weeks of treatment with risperidone

Healthy, psychosis-free controls who will not receive risperidone

Outcomes

Primary Outcome Measures

Change in biomarkers of treatment response: Dorsal Caudate (DCA) GABA levels

Dorsal Caudate (DCA) GABA levels will be ascertained at baseline and after 4 weeks of treatment using MRI scan with 1H MRS to assess treatment response.

Change in biomarkers of treatment response: Dorsal Caudate (DCA) Glutamate

Dorsal Caudate (DCA) Glutamate levels will be ascertained at baseline and after 4 weeks of treatment using MRI scan with 1H MRS to assess treatment response.

Change in biomarkers reflecting treatment response: Medial Prefrontal Cortex (MPFC) GABA

Medial Prefrontal Cortex (MPFC) GABA levels will be ascertained at baseline and after 4 weeks of treatment using MRI scan with 1H MRS to assess treatment response.

Change in biomarkers reflecting treatment response: Medial Prefrontal Cortex (MPFC) Glutamate

Medial Prefrontal Cortex (MPFC) Glutamate levels will be ascertained at baseline and after 4 weeks of treatment using MRI scan with 1H MRS to assess treatment response.

Secondary Outcome Measures

Changes in neurocognitive performance: MATRICS Consensus Cognitive Battery (MCCB)

Memory, attention, reasoning, emotional intelligence, and verbal ability will be assessed using the MCCB before and after 4 weeks of treatment.

Changes in everyday functioning: University of California San Diego (UCSD) Performance-based Skills Assessment (UPSA)

Ability to function in a variety of everyday tasks from six domains (Financial Skills, Communication, Comprehension/Planning, Transportation, Household Management and Medication Management) will be assessed using the University of California San Diego Performance-based Skills Assessment (UPSA) before and after 4 weeks of treatment.

Changes in clinical symptomatology: Positive and Negative Syndrome Scale (PANSS)

Changes in Positive and Negative Symptoms will be assessed across the treatment period using the PANSS. Participants are rated on a scale of (Absent) (Minimal) (Mild) (Moderate) (Moderate severe) (Severe) (Extreme) to describe Positive, Negative and General symptomatology. Items from each subscale (Positive, Negative, and General) are summed for their respective scales, with lower numbers indicating less severe or absent symptomatology, and higher scores indicating more severe symptoms. A total sum of all subscales is also computed to reflect overall symptom severity. Positive Subscale: 7 items, minimum score = 7, maximum score = 49 Negative Subscale: 7 items, minimum score = 7, maximum score = 49 General Subscale: '16 items, minimum score = 16, maximum score = 112 Total Score: 30 items, minimum score = 30, maximum score = 210.

Changes in motor symptomatology: Abnormal Involuntary Movement Scale (AIMS)

Changes in motor symptomatology associated with tardive dyskinesia (TD) assessed using the Abnormal Involuntary Movement Scale (AIMS). The measure consists of 14 items with scale 0 None Minimal Mild Moderate Severe Higher ratings -> higher levels of motor symptoms. Items 1-7 assess abnormal movements for parts of the body. Ratings are summed to produce a score of total motor symptomatology (min 0, max 28). Item 8 = rating of overall symptom severity based on observation, using the same scale as above. Item 9 = rating of the incapacity of the subject due to abnormal movements, using the same scale as above. Item 10 = rating of the level of awareness and distress in the participant over the abnormal movements, with 0 =No Awareness = Aware, no distress = ~, mild ~ = ~, moderate ~ = ~, severe ~ Item 11-13 = yes/no, rule out dental problems that can lead to a mistaken diagnosis of TD. Item 14 = yes/no if symptoms disappear or persist during sleep.

Changes in clinical severity: Clinical Global Impression Scale

Changes in clinical severity over the course of treatment will be monitored using the The Clinical Global Impression Scale (CGI) consists of two items.- Severity scale (CGI-S). Severity - The first item assesses the patient's current level of mental health symptomatology compared to the clinician's experience with other patients with the same diagnosis. The scale ranges from (Normal, not at all ill) (Borderline mentally ill) (Mildly ill) (Moderately ill) (Markedly ill) (Severely ill) (Among the most extremely ill patients) Improvement - The second item assesses how much the patient's symptomatology has changed since the last clinical visit. Very much improved Much improved Minimally improved No change Minimally worse Much worse Very much worse

Changes in global functioning: Global Assessment of Functioning (GAF)

Changes in global functioning over the course of treatment will be assessed using the Global Assessment of Functioning (GAF). Participants are rated 1-100 on their level of functioning, according to clinical observation: 91 - 100 No symptoms. 81 - 90 Absent or minimal symptoms 71 - 80 If symptoms are present, they expected reactions to stressors 61 - 70 Some mild symptoms 51 - 60 Moderate symptoms 41 - 50 Serious symptoms 31 - 40 Impairment in reality testing or communication or major impairment in several areas 21-30 Behavior influenced by delusions or hallucinations or serious impairment in communication/judgment/inability to function in almost all areas 11-20 Some danger of hurting self or others or occasionally fails to maintain minimal personal hygiene or gross impairment in communication 1-10 Persistent violence risk or lack of self-care 0 No info

Recreational Substances Used by Patients as Recorded by the Substance Use Questionnaire

This measure is a self-reported questionnaire which assesses for any use of the following substances within the past month prior to the initial research visit Tobacco (if the respondent indicates that they have used tobacco in the past month, they are additionally asked, "On average, how many cigarettes per day have you smoked in the past 7 days?" Alcohol, Cocaine, Marijuana, Opiates, Amphetamines, PCP Other Drugs of Abuse (if the respondent indicates they have used other drugs of abuse within the past month of the initial research visit, they are given the opportunity to "specify" which other drugs of abuse they used

Participants' Verbal I.Q as Assessed by the WTAR to Determine Clinical Eligibility

This measure assesses a participant's verbal ability to determine whether they are cognitively able to complete the measures involved in the study. The participant will read from a list of 50 English words and the rater will record whether the pronunciation was correct on a score card for each word spoken. A standard score below the 70th percentile on this measure is indicative of an intellectual disability which would exclude a participant from being clinically and cognitively eligible to complete this study.

Participants' Self-Reported Handedness as Recorded by the Edinburgh Handedness Scale

This measure assesses a participant's preference regarding which hand they would use to complete a specific task. They have the option to indicate whether they would use they would always or most of the time use their left, right, or both left and right hands to complete each task. This measure assesses handedness based on the amount of responses which indicate the participant is either left handed, right handed, or ambidextrous.

Full Information

NCT ID

NCT03323437

First Posted

October 2, 2017

Last Updated

July 24, 2023

Sponsor

Weill Medical College of Cornell University

Collaborators

New York State Psychiatric Institute, Columbia University, National Institute of Mental Health (NIMH)

1. Study Identification

Unique Protocol Identification Number

NCT03323437

Brief Title

Biomarkers of Conversion Risk and Treatment Response in Early-Stage Schizophrenia

Official Title

Biomarkers of Conversion Risk and Treatment Response in Early-Stage Schizophrenia

Study Type

Interventional

2. Study Status

Record Verification Date

July 2023

Overall Recruitment Status

Completed

Study Start Date

September 15, 2017 (Actual)

Primary Completion Date

May 31, 2023 (Actual)

Study Completion Date

May 31, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Weill Medical College of Cornell University

Collaborators

New York State Psychiatric Institute, Columbia University, National Institute of Mental Health (NIMH)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Schizophrenia (SZ) is a highly debilitating neuropsychiatric disorder of young adulthood onset and a leading cause of disability worldwide. While treatments delivered at early stages of the disorder may be effective at reducing psychosis or altering the course of the disease, there are currently no biomarkers capable of identifying subjects in early stages of SZ who are likely to respond to treatment and would be good candidates for available proactive, symptomatic or future disease-modifying treatments; or those who would not respond and can be spared unnecessary medication exposure. The lack of these vitally important biomarkers provides a compelling rationale for the present multidisciplinary research project, which aims to develop and validate highly promising noninvasive and objective proton magnetic resonance spectroscopy (1H MRS)-based biomarkers for monitoring treatment response in early stages of SZ. In support of the viability of this overall objective is a large body of data, reported by the applicants and others, that show (a) that levels of glutamate (Glu) and - aminobutyric acid (GABA) - respectively, the major excitatory and inhibitory amino acid neurotransmitter systems - are abnormally elevated in medication-naïve and unmedicated first episode and chronic SZ patients; (b) that the effect of treatment with antipsychotic medications in these populations may be to lower or normalize brain levels of both Glu and GABA. To investigate the potential of these in vivo brain Glu and GABA abnormalities to serve as biomarkers of treatment response in early-stage SZ, the applicants propose to use 1H MRS to measure Glu and GABA levels in the largest cohort of medication-free SZ subjects to date, at baseline and following 4 weeks of antipsychotic treatment.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Schizophrenia Spectrum and Other Psychotic Disorders

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

47 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Patient

Arm Type

Experimental

Arm Description

Medication-free individuals during first-episode of psychosis who will receive 4 weeks of treatment with risperidone

Arm Title

Control

Arm Type

No Intervention

Arm Description

Healthy, psychosis-free controls who will not receive risperidone

Intervention Type

Drug

Intervention Name(s)

Risperidone

Intervention Description

Participants will meet with a study doctor physician once per week (about 3 times total) to monitor progress and side-effects of risperidone, which includes taking 4 assessments each time. After 4 weeks of taking Risperidone, participant will be assessed and scanned with the MRI/MRS scanner again.

Primary Outcome Measure Information:

Title

Change in biomarkers of treatment response: Dorsal Caudate (DCA) GABA levels

Description

Dorsal Caudate (DCA) GABA levels will be ascertained at baseline and after 4 weeks of treatment using MRI scan with 1H MRS to assess treatment response.

Time Frame

Baseline and 4 weeks of treatment

Title

Change in biomarkers of treatment response: Dorsal Caudate (DCA) Glutamate

Description

Dorsal Caudate (DCA) Glutamate levels will be ascertained at baseline and after 4 weeks of treatment using MRI scan with 1H MRS to assess treatment response.

Time Frame

Baseline and 4th week of treatment

Title

Change in biomarkers reflecting treatment response: Medial Prefrontal Cortex (MPFC) GABA

Description

Medial Prefrontal Cortex (MPFC) GABA levels will be ascertained at baseline and after 4 weeks of treatment using MRI scan with 1H MRS to assess treatment response.

Time Frame

Baseline and 4th week of treatment

Title

Change in biomarkers reflecting treatment response: Medial Prefrontal Cortex (MPFC) Glutamate

Description

Medial Prefrontal Cortex (MPFC) Glutamate levels will be ascertained at baseline and after 4 weeks of treatment using MRI scan with 1H MRS to assess treatment response.

Time Frame

Baseline and 4th week of treatment

Secondary Outcome Measure Information:

Title

Changes in neurocognitive performance: MATRICS Consensus Cognitive Battery (MCCB)

Description

Memory, attention, reasoning, emotional intelligence, and verbal ability will be assessed using the MCCB before and after 4 weeks of treatment.

Time Frame

Baseline and 4th week of of treatment

Title

Changes in everyday functioning: University of California San Diego (UCSD) Performance-based Skills Assessment (UPSA)

Description

Time Frame

Baseline and 4th week of treatment

Title

Changes in clinical symptomatology: Positive and Negative Syndrome Scale (PANSS)

Description

Time Frame

Treatment week 1, treatment week 2, treatment week 3

Title

Changes in motor symptomatology: Abnormal Involuntary Movement Scale (AIMS)

Description

Time Frame

Treatment week 1, treatment week 2, treatment week 3

Title

Changes in clinical severity: Clinical Global Impression Scale

Description

Time Frame

treatment week 1, treatment week 2, treatment week 3

Title

Changes in global functioning: Global Assessment of Functioning (GAF)

Description

Time Frame

Treatment week 1, treatment week 2, treatment week 3

Title

Recreational Substances Used by Patients as Recorded by the Substance Use Questionnaire

Description

Time Frame

This measure is administered on Day 1 of the study.

Title

Participants' Verbal I.Q as Assessed by the WTAR to Determine Clinical Eligibility

Description

Time Frame

This measure is completed on Day 1 of the study.

Title

Participants' Self-Reported Handedness as Recorded by the Edinburgh Handedness Scale

Description

Time Frame

This measure is completed on Day 1 of the study.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

35 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria (Patients): Male or females between the ages of 18-35 less than five years (<60 months) of active Diagnostic and Statistical Manual of Mental Disorders (DSM) diagnosis of schizophrenia, schizophreniform, or schizoaffective disorder Capacity to provide informed consent No major medical or neurological illness Medication free (3 weeks without antipsychotic medications) Exclusion Criteria (Patients): Current alcohol or drug abuse (<1 month) or substance dependence (<6 months) or substances used within one day of the imaging study. Pregnant or lactating women or women of child-bearing potential, who are either not surgically-sterile or, for outpatients, not using appropriate methods of birth control. Intelligence Quotient (IQ) <70 Acute risk for suicide or violence Presence of pacemaker or any metallic objects in the body that would interfere with the MRS or cause MRI safety problems Claustrophobia Any organic brain disorder (including epilepsy, mental retardation, or a medical condition whose pathology or treatment would likely alter the presentation or treatment of SZ Individuals on anti-epileptic medications (e.g., valproate, carbamazepine) that may affect GABA or Glu Unstable medical or neurological condition DSM-V diagnosis of bipolar disorder I DSM-V diagnosis of major depression with psychotic features History of non-response to or non-tolerance of Risperidone Inclusion Criteria (Healthy Controls) Male or females between the ages of 18-35 less than five years (<60 months) of active DSM diagnosis of schizophrenia, schizophreniform, or schizoaffective disorder No major medical or neurological illness Exclusion Criteria (Healthy Controls) Current alcohol or drug abuse (<1 month) or substance dependence (<6 months) or substances used within one day of the imaging study. Pregnant or lactating women or women of child-bearing potential, who are either not surgically-sterile or, for outpatients, not using appropriate methods of birth control. IQ<70 Acute risk for suicide or violence Presence of pacemaker or any metallic objects in the body that would interfere with the MRS or cause MRI safety problems Claustrophobia History of psychotropic medication use such as antipsychotics or antidepressants Any first-degree family history of psychotic illness Personal history of any DSM Axis I disorder Individuals on anti-epileptic medications (e.g., valproate, carbamazepine) that may affect GABA or Glu Unstable medical or neurological condition Any organic brain disorder (including epilepsy, mental retardation, or a medical condition whose pathology or treatment would likely alter the presentation or treatment of SZ

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Dikoma C. Shungu, Ph.D.

Organizational Affiliation

Weill Medical College of Cornell University

Official's Role

Principal Investigator

Facility Information:

Facility Name

New York State Psychiatric Institute & Columbia University

City

New York

State/Province

New York

ZIP/Postal Code

10032

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Undecided

Citations:

PubMed Identifier

9619147

Citation

Abi-Dargham A, Gil R, Krystal J, Baldwin RM, Seibyl JP, Bowers M, van Dyck CH, Charney DS, Innis RB, Laruelle M. Increased striatal dopamine transmission in schizophrenia: confirmation in a second cohort. Am J Psychiatry. 1998 Jun;155(6):761-7. doi: 10.1176/ajp.155.6.761.

Results Reference

background

PubMed Identifier

11264457

Citation

Carlsson A, Waters N, Holm-Waters S, Tedroff J, Nilsson M, Carlsson ML. Interactions between monoamines, glutamate, and GABA in schizophrenia: new evidence. Annu Rev Pharmacol Toxicol. 2001;41:237-60. doi: 10.1146/annurev.pharmtox.41.1.237.

Results Reference

background

PubMed Identifier

14060771

Citation

CARLSSON A, LINDQVIST M. EFFECT OF CHLORPROMAZINE OR HALOPERIDOL ON FORMATION OF 3METHOXYTYRAMINE AND NORMETANEPHRINE IN MOUSE BRAIN. Acta Pharmacol Toxicol (Copenh). 1963;20:140-4. doi: 10.1111/j.1600-0773.1963.tb01730.x. No abstract available.

Results Reference

background

PubMed Identifier

9384954

Citation

Coyle JT. The glutamatergic dysfunction hypothesis for schizophrenia. Harv Rev Psychiatry. 1996 Jan-Feb;3(5):241-53. doi: 10.3109/10673229609017192.

Results Reference

background

PubMed Identifier

1681750

Citation

Davis KL, Kahn RS, Ko G, Davidson M. Dopamine in schizophrenia: a review and reconceptualization. Am J Psychiatry. 1991 Nov;148(11):1474-86. doi: 10.1176/ajp.148.11.1474.

Results Reference

background

PubMed Identifier

19233621

Citation

Farooq S, Large M, Nielssen O, Waheed W. The relationship between the duration of untreated psychosis and outcome in low-and-middle income countries: a systematic review and meta analysis. Schizophr Res. 2009 Apr;109(1-3):15-23. doi: 10.1016/j.schres.2009.01.008. Epub 2009 Feb 23.

Results Reference

background

PubMed Identifier

22393215

Citation

Fusar-Poli P, Bonoldi I, Yung AR, Borgwardt S, Kempton MJ, Valmaggia L, Barale F, Caverzasi E, McGuire P. Predicting psychosis: meta-analysis of transition outcomes in individuals at high clinical risk. Arch Gen Psychiatry. 2012 Mar;69(3):220-9. doi: 10.1001/archgenpsychiatry.2011.1472.

Results Reference

background

PubMed Identifier

23165428

Citation

Fusar-Poli P, Borgwardt S, Bechdolf A, Addington J, Riecher-Rossler A, Schultze-Lutter F, Keshavan M, Wood S, Ruhrmann S, Seidman LJ, Valmaggia L, Cannon T, Velthorst E, De Haan L, Cornblatt B, Bonoldi I, Birchwood M, McGlashan T, Carpenter W, McGorry P, Klosterkotter J, McGuire P, Yung A. The psychosis high-risk state: a comprehensive state-of-the-art review. JAMA Psychiatry. 2013 Jan;70(1):107-20. doi: 10.1001/jamapsychiatry.2013.269.

Results Reference

background

PubMed Identifier

1654746

Citation

Javitt DC, Zukin SR. Recent advances in the phencyclidine model of schizophrenia. Am J Psychiatry. 1991 Oct;148(10):1301-8. doi: 10.1176/ajp.148.10.1301.

Results Reference

background

PubMed Identifier

8122957

Citation

Krystal JH, Karper LP, Seibyl JP, Freeman GK, Delaney R, Bremner JD, Heninger GR, Bowers MB Jr, Charney DS. Subanesthetic effects of the noncompetitive NMDA antagonist, ketamine, in humans. Psychotomimetic, perceptual, cognitive, and neuroendocrine responses. Arch Gen Psychiatry. 1994 Mar;51(3):199-214. doi: 10.1001/archpsyc.1994.03950030035004.

Results Reference

background

PubMed Identifier

17942737

Citation

Lodge DJ, Grace AA. Aberrant hippocampal activity underlies the dopamine dysregulation in an animal model of schizophrenia. J Neurosci. 2007 Oct 17;27(42):11424-30. doi: 10.1523/JNEUROSCI.2847-07.2007.

Results Reference

background

PubMed Identifier

10667612

Citation

Laruelle M, Abi-Dargham A. Dopamine as the wind of the psychotic fire: new evidence from brain imaging studies. J Psychopharmacol. 1999 Dec;13(4):358-71. doi: 10.1177/026988119901300405.

Results Reference

background

PubMed Identifier

8799184

Citation

Laruelle M, Abi-Dargham A, van Dyck CH, Gil R, D'Souza CD, Erdos J, McCance E, Rosenblatt W, Fingado C, Zoghbi SS, Baldwin RM, Seibyl JP, Krystal JH, Charney DS, Innis RB. Single photon emission computerized tomography imaging of amphetamine-induced dopamine release in drug-free schizophrenic subjects. Proc Natl Acad Sci U S A. 1996 Aug 20;93(17):9235-40. doi: 10.1073/pnas.93.17.9235.

Results Reference

background

PubMed Identifier

9092613

Citation

Moghaddam B, Adams B, Verma A, Daly D. Activation of glutamatergic neurotransmission by ketamine: a novel step in the pathway from NMDA receptor blockade to dopaminergic and cognitive disruptions associated with the prefrontal cortex. J Neurosci. 1997 Apr 15;17(8):2921-7. doi: 10.1523/JNEUROSCI.17-08-02921.1997.

Results Reference

background

PubMed Identifier

7492260

Citation

Olney JW, Farber NB. Glutamate receptor dysfunction and schizophrenia. Arch Gen Psychiatry. 1995 Dec;52(12):998-1007. doi: 10.1001/archpsyc.1995.03950240016004.

Results Reference

background

PubMed Identifier

16638070

Citation

Olsen KA, Rosenbaum B. Prospective investigations of the prodromal state of schizophrenia: review of studies. Acta Psychiatr Scand. 2006 Apr;113(4):247-72. doi: 10.1111/j.1600-0447.2005.00697.x.

Results Reference

background

PubMed Identifier

16199825

Citation

Perkins DO, Gu H, Boteva K, Lieberman JA. Relationship between duration of untreated psychosis and outcome in first-episode schizophrenia: a critical review and meta-analysis. Am J Psychiatry. 2005 Oct;162(10):1785-804. doi: 10.1176/appi.ajp.162.10.1785.

Results Reference

background

PubMed Identifier

1251927

Citation

Snyder SH. The dopamine hypothesis of schizophrenia: focus on the dopamine receptor. Am J Psychiatry. 1976 Feb;133(2):197-202. doi: 10.1176/ajp.133.2.197.

Results Reference

background

PubMed Identifier

9444480

Citation

Tamminga CA. Schizophrenia and glutamatergic transmission. Crit Rev Neurobiol. 1998;12(1-2):21-36. doi: 10.1615/critrevneurobiol.v12.i1-2.20.

Results Reference

background

PubMed Identifier

8866763

Citation

Tamminga CA, Holcomb HH, Gao XM, Lahti AC. Glutamate pharmacology and the treatment of schizophrenia: current status and future directions. Int Clin Psychopharmacol. 1995 Sep;10 Suppl 3:29-37.

Results Reference

background

PubMed Identifier

17404389

Citation

Yung AR, Yuen HP, Berger G, Francey S, Hung TC, Nelson B, Phillips L, McGorry P. Declining transition rate in ultra high risk (prodromal) services: dilution or reduction of risk? Schizophr Bull. 2007 May;33(3):673-81. doi: 10.1093/schbul/sbm015. Epub 2007 Apr 2.

Results Reference

background

Learn more about this trial

Biomarkers of Conversion Risk and Treatment Response in Early-Stage Schizophrenia

We'll reach out to this number within 24 hrs