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Bipolar Disorder Research and New Medicine Trials

Magnetic Resonance Imaging (MRI) of Neuropsychiatric Patients and Healthy Volunteers

This study is currently recruiting patients.

Sponsored by: National Institute of Mental Health (NIMH)
Information provided by: Warren G Magnuson Clinical Center (CC)

Purpose

The purpose of this study is to use brain imaging technology to compare differences in brain structure, chemistry, and functioning in individuals with brain and mental disorders compared to healthy volunteers.

Schizophrenia is a brain disorder that results from subtle changes and abnormalities in neurons. These deficits likely occur in localized regions of the brain and may result in widespread, devastating consequences. The neuronal abnormalities are inherited through a complex combination of genetic and environmental factors. Brain imaging technologies can be used to better characterize brain changes in individuals with schizophrenia. This study will use magnetic resonance imaging (MRI) scans to identify predictable, quantifiable abnormalities in neurophysiology, neurochemistry and neuroanatomy that characterize schizophrenia and other neurological and neuropsychiatric disorders.

Condition
Bipolar Disorder
Healthy
Mood Disorder
Parkinson's Disease
Schizophrenia

MedlinePlus related topics:  Bipolar Disorder;   Mental Health;   Parkinson's Disease;   Schizophrenia

Study Type: Observational
Study Design: Natural History

Official Title: Structural and Functional Imaging of Neuropsychiatric Patients and Normal Volunteers with 3.0 Tesla MRI and Magnetoencephalography

Further Study Details: 

Expected Total Enrollment:  880

Study start: February 11, 2000

This protocol is meant to provide a matrix for multiple, simultaneous brain imaging investigations using magnetic resonance imaging (MRI) at 3.0 Tesla (3T). We intend to study regional brain structure, physiology, and biochemistry in living human subjects, both healthy and ill. Based on multiple clinical, neuropathological, and functional neuroimaging studies, it is clear that schizophrenia is a brain disorder arising from subtle neuronal deficits (for lack of more specific terminology). These deficits likely arise in a few key regions such as dorsolateral prefrontal cortex and hippocampal formation, that result in widespread, multifaceted, and devastating clinical consequences. These neuronal deficits are clearly heritable, although in a complex fashion from multiple genes interacting in an epistatic fashion with each other and the environment. We hypothesize that these neuronal deficits, clearly resulting in quantifiable behavioral abnormalities in schizophrenic patients, will produce predictable, quantifiable aberrations in neurophysiology that we can "map" using magnetic resonance imaging. In spite of numerous functional imaging findings, clinical applications remain scarce and pathognomic findings absent. Therefore, we do not anticipate that an approach based solely on any one modality is likely to significantly advance our knowledge base. Instead, we propose to create brain imaging datasets for individual human subjects predicated on 1) the appraisal of brain function from multiple domains simultaneously; 2) the characterization of brain function via summation and intercorrelation of these data; and 3) the digestion of these data based on the parsing of complex clinical phenomenology into quantifiable neurophysiological parameters. Thus, in addition to the identification of those parameters that best characterize and identify manifest schizophrenia (i.e., state variables), we hypothesize that some of these fundamental characteristics will be heritable. These fundamental characteristics, so-called endo- or intermediate phenotypes, represent powerful tools to find susceptibility genes and have already generated a number of linkage findings.

Eligibility

Genders Eligible for Study:  Both

Accepts Healthy Volunteers

Criteria

INCLUSION CRITERIA:
Patients and volunteers of any sex, race or ethnicity will be recruited.
CONTROLS:
No psychiatric or severe chronic medical illness at the time of the study, and by history. This includes the absence of substance abuse histories, learning disabilities and all DSM IV disorders. Investigators will evaluate histories and medical conditions that are judged not to interfere with the study.
No use of psychotropic substances in the last 3 months.
There is no upper age limit. The lower age limit is 18 years.
PATIENTS:
Schizophrenia, any subtype or schizo-affective disorder according to DSM IV .
Bipolar Disorder with Psychotic Features according to DSM IV.
Menstrually-Related Mood Disorder.
Mild to moderate Parkinson's Disease (Hoehn and Yahr Stage 1-3).
William's Syndrome (partial or full).
Patients with Multiple Sclerosis.
EXCLUSION CRITERIA:
CONTROLS AND PATIENTS:
Impaired hearing.
Pregnancy.
Head trauma with loss of consciousness in the last year, or any evidence of functional impairment due to and persisting after head trauma.
Patients or healthy volunteers with known risk from exposure to high magnetic fields (e.g. patients with pace makers) and those who have metallic implants (e.g. braces) in the head region (likely to create artifact on the MRI scans) will be excluded from participating in the fMRI studies.
PATIENTS:
Coexistence of another major mental illness at the time of the study.
Criteria for substance abuse met in the last 6 months.
Criteria for substance dependence met in the last year. The duration of the dependency must be less than 3 years and not judged to have produced long-term brain changes.
Major concurrent medical illness likely to interfere with acquisition of the task.
Concomitant medications which could interfere with performance on the task.
Presence of dyskinetic movements of the face and tongue (likely to interfere with eyeblink measures), or of gross involuntary movements of the whole body (likely to interfere with positioning in the MRI scanner).
Pregnant or lactating woemn will be excluded from studies.
All patients smoking or drinking coffee will be asked to refrain 4 hours prior to the study.

Location and Contact Information


Maryland
      National Institute of Mental Health (NIMH), 9000 Rockville Pike,  Bethesda,  Maryland,  20892,  United States; Recruiting
Bobby Das  3014354593    bdas@ln.nimh.nih.gov 

More Information

Detailed Web Page

Publications

Weinberger DR. Implications of normal brain development for the pathogenesis of schizophrenia. Arch Gen Psychiatry. 1987 Jul;44(7):660-9.

Kidd KK. Can we find genes for schizophrenia? Am J Med Genet. 1997 Feb 21;74(1):104-11. No abstract available.

Risch N, Merikangas K. The future of genetic studies of complex human diseases. Science. 1996 Sep 13;273(5281):1516-7. No abstract available.

Study ID Numbers:  000085; 00-M-0085
Record last reviewed:  February 12, 2004
Last Updated:  February 12, 2004
Record first received:  February 15, 2000
ClinicalTrials.gov Identifier:  NCT00004571
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2004-10-27

FMRI Study of Performance During a Probabilistic Reversal Learning Task in Depression

This study is currently recruiting patients.

Sponsored by: National Institute of Mental Health (NIMH)
Information provided by: Warren G Magnuson Clinical Center (CC)

Purpose

This study will examine how the brains of depressed people function during learning and respond to feedback. Participants perform a "probabilistic reversal learning task" to determine whether depressed people perform worse on a task than non-depressed people when they sometimes receive misleading negative feedback.

Right-handed healthy volunteers, people with major depression who are currently depressed or have previously been depressed and people with bipolar depression between 18 and 50 years of age may be eligible for this study. Candidates are screened with a medical and psychiatric history, physical examination, electrocardiogram, blood and urine tests. They are also interviewed to evaluate mood, sleep, energy, work and school performance, and social relationships, and asked to answer questions to investigate whether any history of paranoia, panic attacks, obsession, compulsions, suicidal thoughts, eating disturbances, and alcohol or drug abuse is present. They complete rating scales for depression, anxiety, and negative thinking; history of alcohol and tobacco use; physical movement; socioeconomic status; overall level of functioning; and depression type. Finally, they undergo a battery of neuropsychological tests to assess general intelligence, handedness, and specific cognitive abilities, including memory and concentration.

Participants perform the probabilistic reversal learning task either in a testing room seated in front of a computer or lying down while undergoing functional magnetic resonance imaging (FMRI). FMRI is a diagnostic test that uses a strong magnet and radio waves to obtain pictures of brain structure and function. For the scan, the subject lies on a narrow bed with a plastic-encased metal coil close to the head. The bed slides into the scanner - a small tunnel about 6 feet long. All subjects, whether in the testing room or in the MRI scanner, undergo the learning task as follows:

Two patterns are presented on a computer screen. One pattern is designated "correct" and the other "incorrect." Subjects are asked to choose the correct pattern on each try and are provided feedback as to whether the response was right or wrong. Sometimes the rule changes, and the pattern that was correct is now wrong, and vice versa, so that the new correct pattern must be chosen. In addition, misleading feedback is sometimes given intentionally, indicating the subject chose the wrong pattern when in fact the response was correct. Subjects should change their response only when they are sure that the rule has changed, and not because they were incorrectly told that they were wrong. For patients undergoing MRI, blood flow in the different areas of the brain is measured during the test.

After the test, outside the scanner, participants undergo additional tests of attention, memory, and concentration like those that were administered during the screening procedures.

Condition
Major Depressive Disorder

MedlinePlus related topics:  Mental Health

Study Type: Observational
Study Design: Natural History

Further Study Details: 

Expected Total Enrollment:  100

Study start: January 5, 2004

When depressed subjects perceive they have failed while performing a neuropsychological task their performance on subsequent trials becomes impaired. Elliott et al. showed that MDD subjects were far more likely to fail on subsequent tasks after failure on one task than controls. This effect has been described as an "abnormal response' to negative feedback or a 'catastrophic response to perceived failure.'

Murphy et al. investigated this further using a probabilistic reversal learning task in which subjects were faced with occasional negative feedback that was actually false. On each trial of the task subjects choose one of two stimuli on screen, one considered correct and the other incorrect, this is followed by feedback. Instructions prior to starting the task inform the subject that sometimes the rule will change and the previously correct stimulus will be incorrect, but sometimes the computer will give them incorrect feedback. They are instructed to switch responding only when they are sure the rule has actually changed. MDD subjects demonstrate intact acquisition and reversal of probabilistic learning but are impaired in their ability to maintain a response in the face of misleading negative feedback. This profile of impairment may be relatively specific to MDD as, for example, it is not found in subjects with other neuropsychiatric conditions. This 'abnormal response' to negative feedback may represent a significant link between negative affect and cognitive impairments in depression.

During the proposed study functional magnetic resonance images will be acquired while subjects perform a version of the probabilistic reversal learning task. Four groups will take part: MDD, bipolar depressed, unmedicated MDD in remission and healthy control subjects. These images will be used to investigate differences in neural activation between the four groups, to clarify whether this specific profile of behavioral response extends to bipolar depressed subjects and to assess the mood state dependences of this effect. This would increase understanding of the specific profile of performance on this task and neural basis of this abnormal response to negative feedback that contributes to impairment of cognitive performance in depression.

Eligibility

Genders Eligible for Study:  Both

Accepts Healthy Volunteers

Criteria

INCLUSION CRITERIA:
All subjects will be between 18 and 50 years old. Male and female subjects will be included. All subjects must be able to give written informed consent prior to participation in this study.
MDD Depressed Sample: Twenty subjects (ages 18-50) male and female will be selected, with primary MDD currently depressed as defined by DSM-IV criteria for recurrent MDD, in a current major depressive episode and who have a first degree relative with MDD but no first degree relatives with mania, alcoholism, or antisocial personality disorder.
MDD Remission Sample: Twenty subjects (ages 18-50) male and female will be selected. Remission is defined as a period of at least three months during which the subject has not taken an antidepressant agent, with Hamilton Depression Rating Scale (HDRS; 21-item; Hamilton 1960) scores in the non-depressed range (less than 8), and with no more than one clinically significant depressive symptom.
Bipolar Depressed Sample: Twenty subjects (ages 18-50) male and female will be selected who meet DSM-IV criteria for bipolar I or II disorder and are currently in a depressed phase.
Healthy Control Sample: Twenty subjects (ages 18-50) male and female who have not met criteria for any major psychiatric disorder will be selected. From this large sample a control subject will be matched to each depressed subject for age, gender, handedness and IQ. The control subjects will have no known first degree relatives with mood disorders.
EXCLUSION CRITERIA:
Individuals with any major medical or neurological disorder or who have received psychotropic drugs or medication likely to influence cerebral blood flow or metabolism within 3 weeks (8 weeks for fluoxetine [Prozac]), of scanning.
Bipolar subjects with rapid cycling or with current psychosis will be excluded from the protocol.
Effective treatment will not be discontinued for the purposes of this protocol, subjects will be identified who have never been treated or who have discontinued medication due to lack of efficacy, noncompliance, physician order or other reasons prior to study entry.
Individuals who meet DSM-IV criteria for alcohol and/or substance abuse within 1 year prior to screening or lifetime history of substance dependence.
Women of childbearing potential who are known to be pregnant or who have a positive pregnancy test.
Individuals who have experienced serious suicidal ideation within the past 2 months.
General exclusions for MRI imaging, such as having had a cardiac pacemaker or ferromagnetic object implanted through surgical intervention or accident (for example: shrapnel).

Location and Contact Information


Maryland
      National Institute of Mental Health (NIMH), 9000 Rockville Pike,  Bethesda,  Maryland,  20892,  United States; Recruiting
Patient Recruitment and Public Liaison Office  1-800-411-1222    prpl@mail.cc.nih.gov 
TTY  1-866-411-1010 

More Information

Detailed Web Page

Publications

Bechara A, Damasio H, Tranel D, Anderson SW. Dissociation Of working memory from decision making within the human prefrontal cortex. J Neurosci. 1998 Jan 1;18(1):428-37.

Bechara A, Damasio AR, Damasio H, Anderson SW. Insensitivity to future consequences following damage to human prefrontal cortex. Cognition. 1994 Apr-Jun;50(1-3):7-15.

BECK AT, WARD CH, MENDELSON M, MOCK J, ERBAUGH J. An inventory for measuring depression. Arch Gen Psychiatry. 1961 Jun;4:561-71. No abstract available.

Study ID Numbers:  040075; 04-M-0075
Record last reviewed:  December 23, 2003
Last Updated:  December 23, 2003
Record first received:  January 8, 2004
ClinicalTrials.gov Identifier:  NCT00075296
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2004-10-27

Comparison of Three Electroconvulsive Therapy (ECT) Techniques for the Treatment of Major Depression

This study is currently recruiting patients.

Sponsored by: National Institute of Mental Health (NIMH)
Information provided by: National Institute of Mental Health (NIMH)

Purpose

The purpose of this study is to compare the antidepressant benefits and cognitive side effects of three different types of electroconvulsive therapy (ECT) in individuals with unipolar or bipolar depression.

Condition Treatment or Intervention
Depression
 Procedure: Electroconvulsive Therapy

MedlinePlus related topics:  Depression

Study Type: Interventional
Study Design: Treatment, Randomized, Double-Blind, Active Control, Parallel Assignment, Safety/Efficacy Study

Official Title: Comparing Three Electrode Placements to Optimize ECT

Further Study Details: 

Expected Total Enrollment:  360

Study start: February 2003;  Study completion: May 2006

ECT is an important treatment for severely depressed people who do not respond adequately to, or are intolerant of, antidepressant medication. Traditionally, ECT has been administered with one of two standard techniques: bilateral and right unilateral electrode placement. However, these techniques are limited by either low efficacy or high cognitive impairment. Recently, an additional technique for ECT administration has shown promise in preliminary studies: bifrontal ECT. This study will compare this technique to the two traditional ECT techniques in treating people with depressive symptoms.

Participants in this study will be randomly assigned to receive standard bilateral ECT, high-dose right unilateral ECT, or bifrontal ECT in their index course. Depression symptoms, neuropsychological status, and quality of life will be measured throughout the course of the ECT treatment, one week after, and at a 2-month follow-up visit. This study will run for 4 years.

Eligibility

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

  • Diagnosis of unipolar or bipolar depression

Location and Contact Information


Minnesota
      Mayo Clinic, Rochester,  Minnesota,  United States; Recruiting
Keith G. Rasmussen, MD  507-284-3789    rasmussen.keith@mayo.edu 
Keith Rasmussen, MD,  Principal Investigator

New Jersey
      UMDNJ, Newark,  New Jersey,  07103,  United States; Recruiting
Charles Kellner, MD  973-972-7117    kellner@umdnj.edu 
Charles Kellner, MD,  Principal Investigator

New York
      Northshore/Long Island Jewish Hillside Hospital, Glen Oaks,  New York,  11004,  United States; Recruiting
Georgios Petrides, MD  718-470-8569    petrides@lij.edu 
Georgios Petrides, MD,  Principal Investigator

Texas
      University of Texas Southwestern Medical Center, Dallas,  Texas,  75235,  United States; Recruiting
Mustafa Husain, MD  214-648-2806    mustafa.husain@utsouthwestern.edu 
Mustafa Husain, MD,  Principal Investigator

More Information

Study ID Numbers:  67201-01
Record last reviewed:  August 2004
Record first received:  September 24, 2003
ClinicalTrials.gov Identifier:  NCT00069407
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2004-10-27

Examination of Brain Serotonin Receptors in Patients with Mood Disorders

This study is currently recruiting patients.

Sponsored by: National Institute of Mental Health (NIMH)
Information provided by: Warren G Magnuson Clinical Center (CC)

Purpose

The purpose of this study is to evaluate the function of certain brain chemicals and receptors in patients with mood disorders. This study will also examine how the stress hormone cortisol affects brain function.

Data suggest that serotonin 1A (5-HT1A) receptor function is abnormal in patients with mood disorders, such as major depressive disorder (MDD) and bipolar disorder (BP). However, these data are limited because they are based on small sample sizes. In this study, PET scans will be used to compare 5-HT1A receptor binding potential between mood disorder patients and healthy volunteers.

All participants will have an initial medical and psychiatric evaluation. Depression severity, anxiety, negative thinking, level of functioning, intelligence, and cognitive functions will be measured. Urine, saliva, and blood will be collected. Women will have a pregnancy test and tests to determine menstrual phase and time of ovulation. Participants will undergo magnetic resonance imaging (MRI) and PET scans of the brain. Some participants will have other procedures such as a lumbar puncture. Participants with Cushing's disease will undergo imaging as a comparison group.

Condition Treatment or Intervention
Mood Disorder
 Drug: 15 O-water
 Drug: FCWAY

MedlinePlus related topics:  Mental Health

Study Type: Observational
Study Design: Natural History

Official Title: Serotonin1A Receptor and Serotonin Transporter Imaging In Mood Disorders

Further Study Details: 

Expected Total Enrollment:  166

Study start: October 4, 2001

Multiple lines of evidence suggest that serotonin1A (5-HT1A) receptor and serotonin transporter (5-HTT) function is abnormal in major depressive disorder (MDD) and that somatic antidepressant treatments effect changes the function of these systems that are relevant to their therapeutic mechanisms. The data supporting these hypotheses have been obtained by assessing neuroendocrine and temperature responses to 5-HT1A agonists in MDD subjects, measuring 5-HT1A receptor and 5-HTT binding in brain tissue acquired post mortem from small samples of MDD subjects, and examining effects on 5-HT1A receptor function in rats following antidepressant drug (AD) administration. The recent development of highly selective 5-HT1A receptor and 5-HTT radioligands for positron emission tomography (PET) imaging made direct, noninvasive exploration of the central serotonin sites binding possible. Two studies conducted using one of these, [carbonyl-11C]-WAY-100635, found reduced 5-HT1A receptor binding potential (BP) in the mesiotemporal cortex, the raphe, and the prefrontal cortex (PFC). Pilot data from these studies suggested that the abnormal reduction in 5-HT1A receptor BP is more prominent in bipolar disorder (BD) than MDD subjects (i.e., unipolar depressives) who did not have bipolar relatives, and that it exists independently of mood state.

However, these data have the limitations that the subject samples studied in these preliminary post mortem and PET series have been small, and that [carbonyl-11C]WAY-100635 uptake is difficult to quantitate in PET images. Therefore, these observations require replication in subject samples large enough to establish main effects of diagnostic subtype using a 5-HT1A receptor radioligand that can be validly quantitated. A selective 5-HT1A receptor radioligand suitable for this purpose, [18F]FC-WAY100635 ([18F]FCWAY), has recently been developed at the NIH. In addition, a recently developed selective 5-HTT ligand, [11C] DASB provides a unique opportunity to image the 5-HTT in the same depressed sample.

The proposed study will advance knowledge regarding the neurobiology of mood disorders by employing PET and [18F]FCWAY and [11C] DASB to compare 5-HT1A receptor BP between mood disordered and healthy control subjects in the mesiotemporal cortex, raphe, anterior cingulate gyrus, and left orbital cortex. The following hypotheses, based upon pilot data acquired using [carbonyl-11C]-WAY-100636, will be tested: 1) Depressives have reduced 5-HT1A receptor binding relative to healthy controls. 2) Bipolar depressives will have significantly greater reductions in 5-HT1A receptor binding than unipolar depressives with only unipolar relatives. A pilot study in which bipolar depressives are treated with lithium or divalproex and then re-imaged will test the third hypothesis, that 5-HT1A receptor binding will increase in bipolar subjects during mood stabilizer therapy.

Finally, because central 5-HT1A receptor density is down-regulated in rodents by corticosterone administration and by stress-mediated corticosterone secretion, assessments of hypothalamic-pituitary-adrenal (HPA) axis activity (which is commonly elevated in MDD and BD), will be assessed to determine whether down-regulation of 5-HT1A receptors correlates with cortisol hypersecretion in mood disorders. Because this down-regulation may play a compensatory role to reduce cortisol secretion, neuroendocrine assessments of long-standing rather than acute hypercortisolism and of the pathophysiological diathesis to hypersecrete cortisol will be emphasized as providing the most sensitive correlates of reduced 5-HT1A receptor binding. A medical control group with Cushing's Disease will also be imaged to determine whether pathological elevation of glucocorticoid levels down-regulates 5-HT1A receptor expression in humans, as it does in rats.

Eligibility

Genders Eligible for Study:  Both

Accepts Healthy Volunteers

Criteria

INCLUSION CRITERIA:
MDD SAMPLES:
Sixty subjects (ages 18 to 60) with MDD will be selected who additionally meet criteria for one of 3 subgroups:
A) MDD, Currently depressed with FPDD, as defined by DSM-IV criteria for recurrent MDD, currently in a major depressive episode, who have a first degree relative with MDD but no first degree relatives with mania, alcoholism, or antisocial personality disorder.
B) MDD, Currently in remission with a history of FPDD, defined as a period of at least six months with no more than one clinically significant symptom, and during which time subjects were not taking an AD agent. Subjects will thus meet the historical criteria for recurrent MDD (DSM-IV). We will also require that subjects previously had a least one antidepressant drug trial, to ensure that the severity of previous episodes warranted treatment.
C) MDD, Currently depressed, non-FPDD. To assess the specificity of the findings in MDD to FPDD, a sample meeting criteria for MDD, currently in a depressive episode, but not FPDD will also be imaged.
BIPOLAR DEPRESSED SAMPLE:
Twenty subjects (ages 18 to 60) who meet DSM-IV criteria for bipolar disorder and are currently in a major depressive episode. Subjects may be inpatients or outpatients. Because effective treatment will not be discontinued for the purposes of this protocol, subjects will be identified who have never been treated or who have discontinued medication due to lack of efficacy, noncompliance, physician order or other reasons prior to study entry.
HEALTHY, LOW RISK, CONTROL SAMPLE:
Forty subjects (ages 18 to 60) who have not met criteria for any major psychiatric disorder. The control subjects will have no known first or second degree relatives with mood disorders.
CUSHINGS DISEASE CONTROL SAMPLE:
Ten subjects (ages 18 to 60) with probable Cushing's Disease will be recruited who have both clinical and biochemical evidence of hypercortisolism (including urinary free cortisol excretion higher than the upper limit of normal (greater than 248) nmole/day, and marked central adiposity, cutaneous atrophy, proximal myopathy, and large purple striae). The diagnosis of probable Cushing's Disease will also have been established prior to referral via CRH and ACTH.
MENSTRUALLY-RELATED DYSPHORIC DISORDER SAMPLE:
(n equals 30; ages 18-50). These females are recruited, screened and diagnosed by collaboration under protocol number 81-M-0126, previously approved by IRB, entitled 'The Phenomenology and Biophysiology of Menstrually Regulated Mood and Behavioral Disorders', principal investigator, David Rubinow, M.D. As described in that protocol these subjects must have a regular menstrual cycle lasting 21 - 33 days and meet the following criteria: 1) history within the last two years of at least six months with menstrually-related mood or behavioral disturbances of at least moderate severity - that is, disturbances that are distinct in appearance and associated with a notable degree of subjective distress; 2) a 30 percent increase in mean negative mood ratings (relative to the range of the scale employed) in the premenstrual week compared with the week following the end of menses in at least two of the three cycles; 3) age 18 to 50; 4) not pregnant and in good medical health; 5) regular menses.
EXCLUSION CRITERIA:
Subjects must not have taken antidepressant or other medications likely to alter monoamine neurochemistry or cerebrovascular function for at least 3 weeks (8 weeks for fluoxetine) prior to scanning. Subjects being scanned at two points or the same point twice in their menstrual cycle must not have taken birth control pills for at least 6 months prior to scanning. However, effective medications will not be discontinued for the purposes of this study. Instead, subjects will be recruited who are not currently receiving psychotropic drugs. Subjects will also be excluded if they have:
a) serious suicidal ideation or behavior;
b) psychosis to the extent that the ability to provide informed consent is in doubt;
c) medical or neurological illnesses likely to affect physiology or anatomy;
d) a history of drug or alcohol abuse within 1 year or a lifetime history of alcohol or drug dependence (DSM IV criteria);
e) current pregnancy
f) current breast feeding;
g) general MRI exclusion criteria;
h) previous exposure to ecstasy (i.e. MDMA) which has neurotoxic effects on 5-HTT expressing neurons.
Subjects beyond age 50 are excluded from the MRMD sample due to peri-menopausal status and subjects beyond age 60 are excluded to reduce the biological heterogeneity encompassed by the MDD criteria, since depressives whose age-at MDD-onset is later than 60 have a far greater likelihood of having MRI correlates of cerebrovascular disease than age-matched, healthy controls or age-matched, early-onset depressives.
Subjects whose first major depressive episodes arose temporarily after other major medical or psychiatric conditions will also be excluded.

Location and Contact Information


Maryland
      National Institute of Mental Health (NIMH), 9000 Rockville Pike,  Bethesda,  Maryland,  20892,  United States; Recruiting
Patient Recruitment and Public Liaison Office  1-800-411-1222    prpl@mail.cc.nih.gov 
TTY  1-866-411-1010 

More Information

Detailed Web Page

Publications

Drevets WC, Frank E, Price JC, Kupfer DJ, Holt D, Greer PJ, Huang Y, Gautier C, Mathis C. PET imaging of serotonin 1A receptor binding in depression. Biol Psychiatry. 1999 Nov 15;46(10):1375-87.

Gunn RN, Sargent PA, Bench CJ, Rabiner EA, Osman S, Pike VW, Hume SP, Grasby PM, Lammertsma AA. Tracer kinetic modeling of the 5-HT1A receptor ligand [carbonyl-11C]WAY-100635 for PET. Neuroimage. 1998 Nov;8(4):426-40.

Sargent PA, Kjaer KH, Bench CJ, Rabiner EA, Messa C, Meyer J, Gunn RN, Grasby PM, Cowen PJ. Brain serotonin1A receptor binding measured by positron emission tomography with [11C]WAY-100635: effects of depression and antidepressant treatment. Arch Gen Psychiatry. 2000 Feb;57(2):174-80.

Study ID Numbers:  020047; 02-M-0047
Record last reviewed:  November 4, 2003
Last Updated:  November 4, 2003
Record first received:  November 14, 2001
ClinicalTrials.gov Identifier:  NCT00026832
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2004-10-27

Severe Mood and Behavioral Dysregulation in Children: Pathophysiology and Treatment with Lithium

This study is currently recruiting patients.

Sponsored by: National Institute of Mental Health (NIMH)
Information provided by: Warren G Magnuson Clinical Center (CC)

Purpose

This study seeks to characterize symptoms of severe mood and behavioral dysregulation (SMBD) in children and adolescents. The study will also evaluate the effectiveness of lithium as a treatment for this condition while subjects participate in day-treatment or inpatient care.

Children with SMBD display chronic anger, sadness, irritability, hyperarousal symptoms (such as insomnia, distractibility) and extreme responses to frustration. Participants will be screened as outpatients using medical and psychiatric history and interview, physical examination, blood and urine tests, and an electrocardiogram.

Children with SMBD have current medications gradually withdrawn over 1- to 3-weeks and then are randomly assigned to receive either lithium or a placebo (sugar pill).

The treatment phase is 8 weeks and is provided on a children's inpatient unit or day treatment center, depending on clinical considerations. All children will receive placebos for at least 2 weeks during some part of the 8-week trial. During treatment, participants are rated on mood, behavior, and medication side effects. Blood tests are obtained weekly or as clinically indicated. At the end of the 8 week randomized trial, children who took placebo may be offered lithium. Children who took lithium but did not respond will be stabilized before returning to care in the community. Schooling is provided in the inpatient and day treatment programs.

Patients receive neuropsychological testing, experimental psychophysiological studies, magnetic resonance imaging (MRI) scans of brain structure, and research magnetic resonance spectroscopy (MRS) scans. . Patients are asked to wear activity monitors on their wrist. Information on family medical and psychiatric history is also obtained.

Patients are asked to return for follow-up visits once every 2 years for repeat interviews, medical, psychiatric and school histories, questionnaires, physical examination, blood work, and structural MRI. Participants will be followed over time and their symptoms will be compared with those of children with bipolar disorder (BPD) and healthy volunteers (controls).

Condition Phase
Mood Disorder
Phase IV

MedlinePlus related topics:  Mental Health

Study Type: Interventional
Study Design: Treatment

Further Study Details: 

Expected Total Enrollment:  350

Study start: October 29, 2001

Recently, researchers and clinicains have focused increased attention on a group of children with severe mood and behavioral dysregulation. These children are characterized by impairing symptoms that include abnormal baseline mood (i.e. irritability, anger, and/or sadness), hyperarousal (e.g. insomnia, agitation, distractibility), and increased reactivity to negative emotional stimuli. Because this syndrome shares many clinical features with bipolar disorder (BPD), there is considerable debate as to whether these children should be diagnosed with BPD. However, children with this syndrome lack the cardinal symptoms of BPD (i.e. euphoria, elation, grandiosity, decreased need for sleep, and increased goal-directed activity). Similrly, while many of these children fit diagnostic criteria for other DSM-IV diagnoses (including attention deficit hyperactivity, oppositional defiant, major depressive and/or conduct disorders), these diagnoses capture heterogeneous clinical populations that include many children who do not exhibit the symptoms noted above. Therefore, the first goal of this project is to identify reliably a group of children with severe mood and behavioral dysregulation in order to characterize them clinically and follow them longitudinally. In addition, since there are no controlled trials to guide treatment of these severely impaired children, we will conduct a double-blinded, placebo controlled trial of lithium. The goals of this trial will be to test the efficacy of lithium, and to investigate whether lithium response, which has been associated with neurotrophic effects and with changes in phosphoinositide signaling in bipolar patients, has similar effects in this group of patients. Finally we will test two preliminary hypotheses regarding the possible pathophysiology of their symptoms. To do so, we will use affect-modulated startle techniques parallel to those being used in a study of children with unequivocal BPD (Protocol # 00-M-0198) as well as functional MRI.

Eligibility

Genders Eligible for Study:  Both

Accepts Healthy Volunteers

Criteria

INCLUSION CRITERIA (all 10 must be met):
1. Ages 7-17
2. Mood symptoms: periods of excessive anger, sadness, and/or irritability are present most days ("highly characteristic").
3. Hyperarousal, as defined by at least three of the following symptoms:
a. insomnia,
b. agitation,
c. distractibility,
d. racing thoughts or flight of ideas,
e. pressured speech,
f. intrusiveness
4. Marked Reactivity: The child frequently exhibits markedly increased reactivity to emotional stimuli that is manifest verbally or behaviorally. For example, the child responds to frustration with extended temper tantrums (inappropriate for age and/or precipitating event), verbal rages, and/or aggression toward people or property.
5. The symptoms in # 2, 3, and 4 above are currently present and have been present for at least 12 months without any symptom-free periods exceeding two months.
6. The mood symptoms and excessive reactivity are severe in at least in one setting (e.g. violent outbursts, assaultiveness at home, school, or with peers). In addition, there are at least mild symptoms (distractibility, intrusiveness) in a second setting.
7. If the child meets DSM-IV criteria for major depressive disorder, he/she must have had an adequate trial of an SSRI antidepressant (defined as four weeks of consecutive treatment in minimally effective doses among adults: paroxetine 20 mg; fluoxetine 20 mg; citalopram 20 mg; fluvoxamine 150 mg; sertraline 50 mg). His/her response to the treatment must have been no more than minimal (i.e. CGI-I greater than 2).
8. If the child meets DSM-IV criteria for attention deficit hyperactivity disorder, he/she must have had an adequate trial of methylphenidate (defined as two consecutive weeks of Ritalin, Metadate, Methylin, or Concerta, at least 30 mg/day if adverse effects present, and at least 60 mg/day if dose not limited by adverse effects), and an adequate trial of amphetamines two consecutive weeks of Adderall 20 mg/day or dextroamphetamine 40 mg/day). His/her response to the treatment must have been no more than minimal (i.e. CGI-I greater than 2).
9. Currently in treatment with a psychiatrist for the symptoms.
10. The child is failing his/her treatment. To meet this criterion:
a) The child's current CGAS score must be less than or equal to 60.
b) The child's psychiatrist must agree that the child's response to his/her current treatment is no more than minimal (i.e. CGI-I greater than 2). According to this criterion, it would be clinically appropriate to change the child's current treatment.
c) On the basis of record review and interviews with child and parent, the research team agrees that the child's response to his/her current treatment is no more than minimal (i.e. CGI-I greater than 2).
INCLUSION CRITERIA - CONTROLS:
Control subjects will be age- and sex- matched to the patients. They will have normal physical and neurological examinations and an identified primary care physician. Both control subjects and their first-degree relatives must be free of current or past psychopathology.
EXCLUSION CRITERIA:
1. The individual exhibits any of these cardinal bipolar symptoms:
Elevated or expansive mood;
Grandiosity or inflated self-esteem;
Decreased need for sleep;
Increase in goal-directed activity (this can result in excessive involvement in pleasurable activities that have a high potential for painful consequences)
2. The symptoms occur in distinct periods lasting more than 4 days , and therefore meet criteria for hypomania or mania.
3. Meets criteria for schizophrenia, schizophreniform disorder, schizoaffective illness, PDD, or PTSD.
4. Meets criteria for substance use disorder in the three months prior to randomization.
5. IQ less than 80
6. The symptoms are due to the direct physiological effects of a drug of abuse, or to a general medical or neurological condition.
7. The patient's symptoms have shown a marked response to current treatment.
8. Currently pregnant or lactating, or sexually active without using a barrier method of contraception.
9. Contraindications to treatment with lithium (e.g. renal, thyroid, cardiac disease, seizure disorder).
10. Previous adequate trial of treatment with lithium that did not have beneficial clinical effects. An adequate trial is defined as at least 6 weeks of treatment with a blood level of greater than or equal to 0.8 mEq/L.
EXCLUSION CRITERIA - CONTROLS:
I.Q. less than 80; ongoing medical illness; neurologic disorder (including seizures); pregnancy; meeting past or present criteria for any diagnosis on the K-SADS-PL(7); meeting the criteria for severe mood and behavioral dysregulation; meeting criterion of post-traumatic stress disorder (exposure to a traumatic event).

Location and Contact Information


Maryland
      National Institute of Mental Health (NIMH), 9000 Rockville Pike,  Bethesda,  Maryland,  20892,  United States; Recruiting
Patient Recruitment and Public Liaison Office  1-800-411-1222    prpl@mail.cc.nih.gov 
TTY  1-866-411-1010 

More Information

Detailed Web Page

Study ID Numbers:  020021; 02-M-0021
Record last reviewed:  October 3, 2003
Last Updated:  October 3, 2003
Record first received:  October 31, 2001
ClinicalTrials.gov Identifier:  NCT00025935
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2004-10-27

Effect of Acetylcholine on Thinking and Emotion in Individuals with Mood Disorders

This study is currently recruiting patients.

Sponsored by: National Institute of Mental Health (NIMH)
Information provided by: Warren G Magnuson Clinical Center (CC)

Purpose

The purpose of this study is to use brain imaging technology to examine the role of a neurotransmitter system in regulating brain activity and cognitive performance in individuals with mood disorders.

The cholinergic system mediates the release of neurotransmitters, including acetylcholine. This system may play a role in the behavioral and cognitive impairment observed in individuals with depression. Evidence suggests that during major depressive episodes, the cholinergic system is hypersensitive to acetylcholine. Agents that enhance the function of acetylcholine-binding receptors called muscarinic receptors increase depressive symptoms in depressed individuals and can produce depressive symptoms in healthy people. Muscarinic antagonists inhibit muscarinic function and may improve the behavioral and cognitive aspects of depression. This study will use functional magnetic resonance imaging (fMRI) scans of the brain to evaluate the effects of a cholinergic antagonist on performance and brain activity in people with major depression.

Participants in this study will be screened with a physical and eye examination; an electrocardiogram (EKG); blood, and urinetests; and neuropsychological tests to assess intelligence, handedness, and cognitive abilities. Participants will be interviewed for a history of psychiatric and medical problems. They will then be enrolled in either a pilot study or an fMRI study. Participants in the pilot study will perform a series of memory and attention tasks in four testing sessions. Participants in the fMRI study will perform similar tasks to those in the pilot study while undergoing fMRI scanning.

Condition
Mood Disorders

MedlinePlus related topics:  Mental Health

Study Type: Observational
Study Design: Natural History

Official Title: Cholinergic Modulation of Cognition and Emotion in Mood Disorders: Functional Neuroimaging Studies

Further Study Details: 

Expected Total Enrollment:  318

Study start: February 27, 2003

The goal of this research project is to evaluate the role of the cholinergic system in behavioral and cognitive symptoms observed in mood disorders in humans, using functional brain neuroimaging techniques. Specific aspects of behavior and cognition are impaired in mood disorders, including selective attention, set-shifting and memory; and there is also evidence that depressed subjects exhibit a mood congruent processing bias whereby they more readily process negatively toned information as compared to positively toned information. This cognitive pattern lends itself to evaluation with functional brain imaging, both in terms of identifying the anatomical correlates of the specific behavioral and cognitive deficits as well as characterizing the effects of pharmacological manipulation.

Attention and memory functions are closely tied to the cholinergic neurotransmitter system. The cholinergic system is one of the neurotransmitter systems implicated in the pathophysiology of mood disorders. Evidence suggests that during major depressive episodes, the cholinergic system is hypersensitive to acetylcholine. Agents that enhance muscarinic cholinergic receptor function increase depressive symptoms in depressed subjects, and can produce symptoms of depression in healthy subjects. The preclinical literature more specifically implicates the muscarinic receptors and indicates that the use of muscarinic antagonists, in the context of animal models of depression, results in improvement in the behavioral analogs of depression.

The proposed project investigates the role of cholinergic neurotransmission in the behavioral and cognitive symptoms observed in the depressed phase of both major depressive disorder (MDD) and bipolar disorder (BD). The studies proposed here will identify anatomical correlates of the mood congruent processing bias, working memory, attention and set-shifting deficits observed in depressed subjects. Further, these studies will evaluate the effects of the cholinergic antagonist, scopolamine, both on the performance deficits and on neural activity in brain regions recruited as subjects perform these tasks.

This approach is expected to reveal how neuromodulators influence processing in brain structures recruited to perform these tasks, both in healthy subjects and in major depressive disorders. The combined use of functional brain imaging and pharmacological manipulation to evaluate the role of neurotransmitter dysfunction in depression may direct us to potential therapeutic approaches.

Eligibility

Genders Eligible for Study:  Both

Accepts Healthy Volunteers

Criteria

INCLUSION CRITERIA
Three groups of right-handed subjects will be recruited for studies under this protocol: unipolar depressives, bipolar depressives and age matched healthy controls. Subjects with both unipolar and bipolar depression appear to exhibit abnormal cholinergic function during the depressed phase (see above), and no differences are hypothesized to exist between MDD and BD depressives herein. However, while BD subjects are more difficult to recruit, the evidence for cholinergic abnormalities has been particularly compelling for BD. Therefore both groups will be recruited.
The presence of inclusion and exclusion criteria will be established using both an unstructured clinical interview with a psychiatrist and the Structured Clinical Interview for DSM-IV (SCID). Family history of mental illness will be obtained from the subject using the Family Interview of Genetic Studies. We will recruit 15 subjects per group per study, including the dose finding study for a total of 90 subjects per group.
Depressed Samples
Subjects (ages 18-45) currently suffering from a major depressive episode falling into one of the following subgroups:
1). Major Depressive Disorder (MDD): Subjects will be selected, with primary MDD currently depressed as defined by DSM-IV criteria for recurrent MDD and current IDS score in the moderately-to-severely depressed range.
2). Bipolar Disorder (BD); Subjects will be selected who meet DSM-IV criteria for bipolar disorder and are currently depressed, with IDS score in the moderately-to-severely depressed range.
Healthy Control Sample
Subjects (ages 18-45) who have not met criteria for any major psychiatric disorder and have no known first-degree relatives with MDD or BD will be selected. Control subjects will be matched to depressed subject for age, gender and education.
EXCLUSION CRITERIA
Subjects will be recruited who are drug-naive or who have not received psychotropic drugs for at least 3 weeks (8 weeks for fluoxetine).
Subjects will also be excluded if they have: a) serious suicidal ideation or behavior, or current delusions or hallucinations, b) inability to provide informed consent, c) medical or neurological illnesses likely to affect physiology or anatomy, d) a history of drug or alcohol abuse within 1 year or a lifetime history of alcohol or drug dependence (DSM IV criteria), e) current or past history of other axis I disorders that preceded the onset of MDD or BD, f) current pregnancy (documented by pregnancy testing prior to scanning), g) current breast feeding, h) general MRI exclusion criteria (including the presence of pacemakers, cochlear implants, surgical clips or metal fragments in their eyes or body parts), i) vision and/or hearing problems severe enough to interfere with testing, j) electrocardiographic evidence of ischemia, arrhythmia, conduction defect, or myocardial infarction, k) current blood pressure of greater than 140 mm Hg or less than 90 mm Hg systolic, or greater than 90 mm Hg diastolic (due to the potential cardiovascular effects of scopolamine and physostigmine), l) clinically significant cerebrovascular or cardiovascular disease, hypertension, congestive heart disease, angina pectoris, advanced arteriosclerosis, gross neurological impairment, hyperthyroidism, known hypersensitivity or idiosyncracy to anticholinergic agents, glaucoma, renal or hepatic impairment, m) current nicotine use (due to the effects of nicotine on the cholinergic system), n) narrow angle glaucoma (due to the possibility of exacerbation of this condition by scopolamine), o) age greater than 45 years (to reduce the biological heterogeneity encompassed by the MDD and BD criteria, since subjects with a late age-at onset for depression have a far greater likelihood of having MRI correlates of cerebrovascular disease than age-matched, healthy controls or age-matched, early-onset depressives), p) exposure within two weeks to medications likely to effect cerebral blood flow and metabolism or likely to interact with anti-cholinergic medications (e.g. narcotics or anti-cholinergic agents)- as verified by history and urine drug screen, q) weight greater than 125 kg, to avoid marked differences in volumes of distribution for scopolamine, r) HIV positive status.

Location and Contact Information


Maryland
      National Institute of Mental Health (NIMH), 9000 Rockville Pike,  Bethesda,  Maryland,  20892,  United States; Recruiting
Patient Recruitment and Public Liaison Office  1-800-411-1222    prpl@mail.cc.nih.gov 
TTY  1-866-411-1010 

More Information

Detailed Web Page

Publications

Elliott R, Rubinsztein JS, Sahakian BJ, Dolan RJ. Selective attention to emotional stimuli in a verbal go/no-go task: an fMRI study. Neuroreport. 2000 Jun 5;11(8):1739-44.

Murphy FC, Sahakian BJ, Rubinsztein JS, Michael A, Rogers RD, Robbins TW, Paykel ES. Emotional bias and inhibitory control processes in mania and depression. Psychol Med. 1999 Nov;29(6):1307-21.

Murray LA, Whitehouse WG, Alloy LB. Mood congruence and depressive deficits in memory: a forced-recall analysis. Memory. 1999 Mar;7(2):175-96.

Study ID Numbers:  030108; 03-M-0108
Record last reviewed:  December 23, 2003
Last Updated:  December 23, 2003
Record first received:  March 6, 2003
ClinicalTrials.gov Identifier:  NCT00055575
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2004-10-27

Treatment of Post Traumatic Stress Disorder in Patients with other Mental Illnesses

This study is currently recruiting patients.

Sponsored by: National Institute of Mental Health (NIMH)
Information provided by: National Institute of Mental Health (NIMH)

Purpose

The purpose of this study is to develop an effective treatment for people with Post Traumatic Stress Disorder (PTSD) along with other mental illnesses.

Condition Treatment or Intervention
Stress Disorders, Post-Traumatic
 Behavior: Cognitive Behavior Treatment

MedlinePlus related topics:  Post-Traumatic Stress Disorder

Study Type: Interventional
Study Design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study

Official Title: Cognitive-Behavioral Treatment of PTSD in SMI Clients

Further Study Details: 

Expected Total Enrollment:  88

Study start: January 2002;  Study completion: December 2004

Despite the progress in treating PTSD in the general population and the elevated prevalence of PTSD in people with severe mental illness (SMI), there are no empirically validated treatments designed for patients with comorbid PTSD. The cognitive behavioral treatment provided in this study may improve knowledge of PTSD, decrease distorted beliefs, reduce PTSD symptoms, and improve quality of life.

Participants are randomly assigned to receive either a cognitive behavioral treatment plus standard care for SMI or standard care alone. The cognitive behavioral treatment incorporates several common features, including psychoeducation, relaxation training, and cognitive restructuring. Standard care for SMI includes medication, case management, and psychosocial treatment. PTSD, psychiatric symptoms, health, quality of life, and substance abuse outcomes are measured. Participants' knowledge of PTSD and beliefs about the world are also measured. Participants are assessed at baseline, post-treatment (16 weeks), and at 3- and 6-month follow-ups.

Eligibility

Ages Eligible for Study:  18 Years   -   65 Years,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

  • Post Traumatic Stress Disorder
  • New Hampshire definition of SMI plus DSM-IV Axis I diagnosis of schizophrenia, schizoaffective disorder, bipolar disorder, or major depression
  • Case management services and contact with a case manager at least twice a week

Exclusion Criteria:

  • Alcohol or drug dependence
  • Hospitalization or suicide attempt in the past 2 months

Location and Contact Information

Kim Mueser, Ph.D.      (603) 271-5226    Kim.T.Mueser@dartmouth.edu
Stan Rosenberg, Ph.D.      (603) 448-0126    Stan.Rosenberg@dartmouth.edu

New Hampshire
      Community Mental Health Centers in NH, Claremont,  New Hampshire,  United States; Recruiting
Kim Mueser, Ph.D.  603-271-5226 
Kim Mueser, Ph.D.,  Principal Investigator

Study chairs or principal investigators

Kim Mueser, Ph.D.,  Principal Investigator,  Dartmouth Medical School   
Stanley Rosenberg, Ph.D.,  Principal Investigator,  Dartmouth Medical School   

More Information

NH-Dartmouth PRC website

Study ID Numbers:  64662-01
Record last reviewed:  September 2004
Record first received:  February 4, 2003
ClinicalTrials.gov Identifier:  NCT00053690
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2004-10-27

Family Intervention for Mental Illness and Substance Abuse

This study is currently recruiting patients.

Sponsored by: National Institute of Mental Health (NIMH)
Information provided by: National Institute of Mental Health (NIMH)

Purpose

The purpose of this study is to establish and evaluate a new family intervention program for individuals with mental illness and substance use disorders and their families.

Condition Treatment or Intervention
Mental Disorders
Substance-Related Disorders
Psychotic Disorders
 Behavior: Family Intervention for Dual Diagnosis

MedlinePlus related topics:  Drug Abuse;   Mental Health;   Prescription Drug Abuse

Study Type: Interventional
Study Design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study

Official Title: Family Intervention for SMI and Substance Use Disorder

Further Study Details: 

Expected Total Enrollment:  140

Study start: April 2002;  Study completion: September 2007

Substance use disorder (SUD) in persons with severe mental illness may worsen the course of psychiatric illness. The loss of family support for individuals with mental illness is a major contributing factor to housing instability, homelessness, and other problems. Despite progress toward integrating mental health and substance abuse services, interventions that improve the course of mental illness while helping the families of the mentally ill are not currently available. Enhancing skills for coping with mental illness may be an effective strategy for treating SUD, decreasing caregiver burden, and improving the long-term outcomes for people with mental illness.

Patients and their families are randomly assigned to either the Family Intervention for Dual Diagnosis (FIDD) program or family psychoeducation. The FIDD program lasts for up to 3 years and includes both single and multiple-family group formats. The family psychoeducation program consists of 6 weekly sessions. Routine assessments are conducted on all patients, and relatives are evaluated on a wide range of outcomes, including substance abuse, hospitalizations, psychiatric symptoms, legal problems, aggression, housing and homelessness, family burden, social support, and quality of life. To determine the effectiveness of the FIDD program, knowledge of mental illness and problem-solving skills are assessed in the families following treatment.

Eligibility

Ages Eligible for Study:  18 Years   -   65 Years,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

  • Have schizophrenia, schizoaffective disorder, or bipolar disorder
  • Have a current substance use disorder (within the past 6 months)
  • Are willing to have at least 4 hours of contact per week with family members or significant others
  • Plan to remain in the community
  • Have family members or significant others who consent to participate in the study and plan to remain in the community

Location and Contact Information

Kim T. Mueser, Ph.D.      (603) 271-5226    Kim.T.Mueser@dartmouth.edu

California
      Pacific Clinics El Camino, Santa Fe Springs,  California,  90670-3691,  United States; Recruiting
Roberto Zarate, Ph.D.  562-949-8455    rzarate@ucla.edu 

Massachusetts
      North Suffolk Mental Health Association, Chelsea,  Massachusetts,  02150,  United States; Recruiting
Corrine Cather, PhD   ccather@partners.org 

Study chairs or principal investigators

Kim T. Mueser, Ph.D.,  Principal Investigator,  Dartmouth Medical School   
Shirley Glynn, Ph.D.,  Principal Investigator,  University of California, Los Angeles   

More Information

NH-Dartmouth PRC website

Publications

Mueser KT, Fox L. A family intervention program for dual disorders. Community Ment Health J. 2002 Jun;38(3):253-70.

Study ID Numbers:  62629-01
Record last reviewed:  August 2004
Record first received:  August 12, 2002
ClinicalTrials.gov Identifier:  NCT00043693
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2004-10-27

Phase I/II Study of Decitabine and Valproic Acid in Relapsed/Refractory Leukemia or Myelodysplastic Syndromes

This study is currently recruiting patients.

Sponsored by: M.D. Anderson Cancer Center
SuperGen
Information provided by: M.D. Anderson Cancer Center

Purpose

Valproic acid is a medication that is currently used in the prevention of seizures, bipolar disorder, and migraine headaches. Researchers hope that it may improve the effects of decitabine. Decitabine is a chemotherapy drug with known activity in leukemia and myelodysplastic syndromes.

Condition Treatment or Intervention Phase
Leukemia
Myelodysplastic Syndromes
 Drug: 5-aza-2'-deoxycytidine (decitabine) (DAC)
 Drug: Valproic Acid
Phase I
Phase II

MedlinePlus related topics:  Bone Marrow Diseases;   Leukemia, Adult Acute;   Leukemia, Adult Chronic;   Leukemia, Childhood

Study Type: Interventional
Study Design: Treatment, Non-Randomized, Open Label, Active Control, Single Group Assignment, Safety/Efficacy Study

Official Title: Phase I/II Study of 5-aza-2'-Deoxycytidine and Valproic Acid in Patients with Relapsed/Refractory Leukemia or Myelodysplastic Syndromes

Further Study Details: 

Expected Total Enrollment:  60

Study start: January 2004

Recent studies have shown synergy between demethylating agents and histone deacetylase inhibitors. It has been shown that both DNA methylation and histone deacetylation work together in affecting gene expression.

Therefore, drugs that inhibit DNA methylation and those that inhibit histone deacetylase can reactivate silenced genes in combination better than they can individually. Decitabine (5 aza-2'deoxycytidine), a drug that produces marked DNA hypomethylator, has demonstrated antileukemic activity at low doses. There are several drugs that have been shown to have histone acetylase activity. One of these is valproic acid that has been used safely for many years as an anti-seizure medication.

Eligibility

Ages Eligible for Study:  2 Years and above,  Genders Eligible for Study:  Both

Criteria

INCLUSION FOR PHASE I COMPONENT OF THE STUDY:

  • Patients with refractory or relapsed: acute myelogenous leukemia (AML), acute lymphocytic leukemia (ALL), and myelodysplastic syndrome (MDS) are eligible. Patients with chronic lymphocytic leukemia (CLL) are eligible if fludarabine based therapy has failed. Patients with chronic myeloid leukemia (CML) are eligible if they have documented hematologic resistance to imatinib mesylate or have not achieved or lost any cytogenetic response to imatinib mesylate after 12 months of therapy.
  • Untreated patients older than 60 years of age with AML or MDS who refuse or are not eligible for frontline chemotherapy, are eligible.
  • Performance status of < 2 by the ECOG scale.
  • Signed informed consent indicating that patients are aware of the investigational nature of this study in keeping with the policies of UTMDACC.
  • Age > 2 years. Valproic acid has been associated with a higher rate of severe liver toxicity in children younger than 2 years.
  • Patients must have been off chemotherapy for 2 weeks prior to entering this study and recovered from the toxic effects of that therapy, unless there is evidence of rapidly progressive disease. Use of hydroxyurea for patients with rapidly proliferative disease is allowed for the first two weeks on therapy. Imatinib mesylate (Gleevec) and anagrelide must also be stopped 2 weeks prior to entering this study.
  • Adequate liver function (bilirubin of < 2mg%, SGPT 3 x ULN) and renal function (creatinine < 2mg%).
  • Women of childbearing potential must practice contraception. Men and women must continue birth control for the duration of the trial.

INCLUSION OF PHASE II PORTION OF THE STUDY:

  • As in the phase I portion buy only patients with AML or high-risk MDS (blasts > or = 10%), including untreated patients older than 60 years of age with AML or MDS who refuse or are not eligible for frontline chemotherapy, will be eligible in this portion of the study.

Exclusions

  • Nursing and pregnant females are excluded.
  • Patients with active and uncontrolled infections are excluded.
  • Patients with a known ornithine transcarbamylase disorder, history of unexplained coma or a family history of ornithine transcarbamylase disorder are excluded from this study.
  • Uncontrolled intercurrent illness including, but not limited to symptomatic congestive heart failure, unstable angina pectoris, pancreatitis, psychiatric illness that would limit compliance with study requirements.
  • Patients with history of hepatitis B, C, alcoholic liver disease or evidence of hepatopathy will be excluded.
  • Patients already receiving valproic acid or receiving other anticonvulsionants will be excluded.
  • Untreated patients younger than 60 years will not be candidates for this study.

Location and Contact Information

Guillermo Garcia-Manero, MD      713-745-3428    ggarciam@mdanderson.org

Texas
      M.D. Anderson Cancer Center, Houston,  Texas,  77030,  United States; Recruiting
Guillermo Garcia-Manero, MD  713-745-3428    ggarciam@mdanderson.org 

More Information

M.D. Anderson Cancer Center's website

Study ID Numbers:  2003-0314
Record last reviewed:  August 2004
Record first received:  December 29, 2003
ClinicalTrials.gov Identifier:  NCT00075010
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2004-10-27

Valproate Response in Aggressive Autistic Adolescents

This study is currently recruiting patients.

Sponsored by: National Institute of Child Health and Human Development (NICHD)
Information provided by: National Institute of Child Health and Human Development (NICHD)

Purpose

This study will examine the effect of valproate, a medication used to treat seizures and bipolar disorder, on aggressive behavior in children and adolescents with autism.

Condition Treatment or Intervention Phase
Autism
 Drug: Valproate
Phase III

MedlinePlus related topics:  Autism

Study Type: Interventional
Study Design: Treatment, Randomized, Double-Blind, Placebo Control, Factorial Assignment, Safety/Efficacy Study

Further Study Details: 

Expected Total Enrollment:  30

Autism is a complex biological disorder that generally lasts throughout a person’s life. It starts before age three and causes delays or problems with many different ways in which a person develops or grows. Some people with autism become very aggressive and can hurt others or themselves. This study will test the hypothesis that aggressive autistic adolescents will show a significantly greater response to valproate maintained at blood levels of 75-100 mcg/ml than to placebo. The study will also assess the safety of valproate in autistic adolescents. This represents the first double-blind study of valproate in mentally retarded/developmentally delayed populations.

Participants in this study will undergo DSM-IV evaluation, the Autism Diagnostic Interview-Revised and Autism Diagnostic Observation Schedule, and baseline blood tests. After baseline screening, all participants will be given a placebo for 1 week. Participants will then be randomized to receive either valproate or placebo for 8 weeks. Dosage adjustment according to blood levels drawn at the end of weeks 2 and 4 will be arranged with parents by a child psychiatrist without breaking the blind. The Aberrant Behavior Check-list-Community (ABC-C) irritability subscale will be the primary measure; the Overt Aggression Scale (OAS), ABC-C hyperactivity subscale, Clinical Global Impressions (CGI) problem severity, Self-Injurious Behavior Questionnaire (SIB-Q), and a valproate side effects checklist will be secondary measures.

Eligibility

Ages Eligible for Study:  6 Years   -   21 Years,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria

  • Autism
  • Lives in the Kansas City area

Exclusion Criteria

  • Psychoactive maintenance medication
  • Degenerative central nervous system disorder
  • Unstable medical illness
  • Seizures in the 6 months prior to study entry
  • History of valproate sensitivity or previous liver disease
  • History of ovarian cysts
  • Low platelet count or raised liver transaminases

Location and Contact Information


Kansas
      Outpatient MR/Autism Clinic, University of Kansas, Kansas City,  Kansas,  66160,  United States; Recruiting
Marilyn Weckbaugh, RN  913-588-1315    mweckbaugh@kumc.edu 

Study chairs or principal investigators

Jessica A. Hellings, M.D.,  Principal Investigator,  University of Kansas   

More Information

Study ID Numbers:  P30HD02528; K08MH01516
Record last reviewed:  June 2003
Record first received:  August 1, 2003
ClinicalTrials.gov Identifier:  NCT00065884
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2004-10-27

Neuropsychiatric Evaluation of Healthy Volunteers and Adults with Schizophrenia

This study is currently recruiting patients.

Sponsored by: National Institute of Mental Health (NIMH)
Information provided by: Warren G Magnuson Clinical Center (CC)

Purpose

The purpose of this study is to evaluate the cognitive processes of participants with schizophrenia, participants with nervous system and mental disorders, and healthy volunteers.

Participants in this study will undergo cognitive tests of attention, memory, attention. Participants with attention deficit hyperactivity disorder (ADHD), traumatic brain injury (TBI), bipolar disorder, and Alzheimer's disease (AD) will be compared with participants with schizophrenia. A group of healthy adults and children will undergo cognitive tests to further delineate the degree of impairment in schizophrenia and neurological disorder participants.

Condition
Brain Injury
Dementia
Healthy
Mental Disorder
Schizophrenia

MedlinePlus related topics:  Dementia;   Head and Brain Injuries;   Mental Health;   Schizophrenia

Study Type: Observational
Study Design: Natural History

Official Title: Neuropsychiatric Evaluation of Normal Subjects and Psychiatric and Neurologic Contrast Groups

Further Study Details: 

Expected Total Enrollment:  810

Study start: August 25, 1992

In this study, we propose to administer cognitive tests to schizophrenic patients and to neurologic patients who will serve as contrast groups for neuropsychological studies of patients with schizophrenia. These include studies of Alzheimers disease to dissociate size and organization of lexicon and ADHD and error patterns on CPT. However, the majority of studies will examine schizophrenia in relation to normal controls.

In addition, we propose to obtain test results from a local sample of normal subjects of varying ages and educational backgrounds to further delineate degree of impairment in these clinical groups. As well as assessing adults we wish to assess normal children. In particular, we wish to identify in children the size of their lexicon and their degree of semantic organization within their lexicon.

Eligibility

Genders Eligible for Study:  Both

Accepts Healthy Volunteers

Criteria

INCLUSION CRITERIA
English-speaking adults between ages 21 to 65, in good health and free from significant substance abuse.
Children between ages 4 to 20 must not have a history of special education, using psychotropic medication in long-term counseling or with a history of seizures, head injury or CNS infections.
Normal controls will be recruited and screened for exclusionary morbidity by interview (e.g., no history of contact with mental health professionals, no history of diagnosable alcohol and/or substance abuse).
Normal controls will be recruited from building employees, local universities, from NIMH rosters, and the general public.
EXCLUSION CRITERIA
Excluded are adults with histories of dementing illness, movement disorder, affective disorders, developmental and/or acquired brain injury. Diagnoses will be made by review of medical records, interview, examination, and in the case of psychiatric diagnoses, a structured interview by SCID.
Advertisement will make clear that the subjects will be asked questions about family psychiatric history and their own history or psychiatric disorder, substance abuse, and neurological disease. Only if the subject answers these negatively will he or she participate in this study.

Location and Contact Information


Maryland
      National Institute of Mental Health (NIMH), 9000 Rockville Pike,  Bethesda,  Maryland,  20892,  United States; Recruiting
Terry E. Goldberg, Ph.D.  3014027810    goldbert@intra.nimh.nih.gov 

More Information

Detailed Web Page

Publications

Goldberg TE, Weinberger DR, Berman KF, Pliskin NH, Podd MH. Further evidence for dementia of the prefrontal type in schizophrenia? A controlled study of teaching the Wisconsin Card Sorting Test. Arch Gen Psychiatry. 1987 Nov;44(11):1008-14.

Seidman LJ. Schizophrenia and brain dysfunction: an integration of recent neurodiagnostic findings. Psychol Bull. 1983 Sep;94(2):195-238. Review. No abstract available.

Weinberger DR, Berman KF, Zec RF. Physiologic dysfunction of dorsolateral prefrontal cortex in schizophrenia. I. Regional cerebral blood flow evidence. Arch Gen Psychiatry. 1986 Feb;43(2):114-24.

Study ID Numbers:  920262; 92-M-0262
Record last reviewed:  October 22, 2003
Last Updated:  October 22, 2003
Record first received:  November 3, 1999
ClinicalTrials.gov Identifier:  NCT00001323
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2004-10-27

 

 


 

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