Cortical GABA Concentrations in Subjects With Primary Insomnia and Depression in Partial Remission With Residual Insomnia

Three groups of subjects (MDD with partial remission and residual insomnia, primary
insomnia, and healthy) will participate in the study. All subjects will complete a telephone
screening, and if appropriate a complete face-to-face evaluation, to determine their
eligibility for the study. All subjects meeting eligibility criteria for the study will
complete a baseline MRS session to evaluate differences in GABA concentrations between the
three groups.

Patient Sample.

- Healthy subjects without insomnia (Group A) (n=10)

- Subjects with primary insomnia (Group B) (n=20)

- Subjects with a history of major depressive disorder and currently in partial
remission but with residual insomnia (Group C) (n=20)

Inclusion Criteria for Primary Insomnia Subjects:

- Males or females between the ages of 25 and 55 years

- Clinical diagnosis of primary insomnia meeting DSM-IV criteria.

- Current insomnia ratings (current Sleep Onset Latency SOL > 30 minutes, Insomnia
Severity Index (ISI) > 14, total sleep time (TST) < 6.5 hrs/night).

- No lifetime history of psychopathology other than primary insomnia.

- No sleep disorders previously identified as related to other conditions including
sleep disordered breathing, restless leg syndrome, periodic limb movement disorder,
chronic pain, gastro-esophageal reflux disease, sleep paralysis, nocturnal seizures,
nocturia, enuresis; also narcolepsy and REM behavior disorders (assessed by clinical
interview and Harvard Center and Cognition Habitual Sleep Survey).

Inclusion Criteria for Depressed Subjects:

- Males or females between the ages of 25 and 55 years

- Clinical diagnosis of major depression meeting DSM-IV criteria in partial remission
(HDRS-8-17), confirmed after semi-structured interview with the SCID and HDRS.

- On monotherapy with a single SSRI medication for a period of at least 6-weeks.

- Remaining symptoms of insomnia (current Sleep Onset Latency (SOL) > 30 minutes,
Insomnia Severity Index (ISI) > 14, TST < 6.5 hrs/night).

- Participation is judged clinically appropriate by treatment team.

- No sleep disorders previously identified as related to other conditions including
sleep disordered breathing, restless leg syndrome, periodic limb movement disorder,
chronic pain, gastro-esophageal reflux disease, sleep paralysis, nocturnal seizures,
nocturia, enuresis; also narcolepsy and REM behavior disorders.

Inclusion Criteria for Healthy Control Subjects:

- Males or females between the ages of 25 and 55 years

- No lifetime history of psychopathology or insomnia (current SOL < 30mins, ISI < 4,
TST > 6.5 hrs)

- At low risk for depression (e.g., no first degree relative with child onset,
recurrent, psychotic or bipolar depression)

Exclusion Criteria for all Subjects:

- History of serious medical or neurological illness

- Signs of major medical or neurological illness on examination or as a result of
laboratory studies

- History of psychoactive substance and/or alcohol dependence or abuse in past
6-months.

- Current use of any psychoactive medication or substance (with the exception of
caffeine, as noted below, and the use of an SSRI in the depressed group), during the
two weeks prior to the initial scan.

- More than the caffeine-equivalent of 3 cups of coffee per day, or any regular (i.e.,
more than 1x/2 weeks) use of caffeine after 7pm.

- Use of benzodiazepines or olanzapine in past 3-months.

- Pregnant or nursing

- Any implanted metal devise or metal fragments