Imaging 5HT7 Antagonist Effects in Bipolar Disorder

Inclusion Criteria:

1. Right-handed participants between the ages of 18 and 60 years, inclusive, who arecurrently in a euthymic mood state defined as ≤8 on the Hamilton Rating Scale forDepression (HAM-D) and Young Mania Rating Scale (YMRS).
2. The participant has a resting pulse ≥51 bpm and ≤100 bpm.
3. The subject has a resting systolic blood pressure ≥91 mmHg and ≤140 mmHg and a restingdiastolic blood pressure ≥51 mmHg and ≤90 mmHg at the Screening Visit. An out-of-rangeresting systolic blood pressure may be repeated if a medically valid reason ispresent, for example, the subject suffers from white-coat hypertension or experiencedstress (e.g. late arrival).The medically valid reason must be documented and signed bythe investigator.
4. The subject has clinical laboratory test values within the reference ranges based onthe blood and urine samples taken at the Screening Visit. Borderline value parametersmay be accepted if they are, in the opinion of the investigator, clinicallyinsignificant.
5. Evidence of a personally signed and dated informed consent document indicating thatthe subject has been informed of all pertinent aspects of the trial.
6. Willing and able to comply with scheduled visits, treatment plan, laboratory tests,and other trial procedures.
7. Ability to understand written and verbal instructions in English.
8. Women of child bearing potential must have a negative pregnancy test at screening andat baseline visits and must agree to use a medically accepted method of contraceptionthroughout the study.

Exclusion Criteria:

1. Evidence or history of clinically significant haematological, renal, endocrine,pulmonary, gastrointestinal, cardiovascular, hepatic, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergiesat time of dosing), and any primary psychiatric diagnosis other than bipolar disorder.
2. Participants who have used or plan to use during the conduct of the study:
3. Fluoxetine within 5 weeks prior to the baseline visit or during the study
4. Monoamine oxidase inhibitors within 3 weeks of the baseline visit or during thestudy
5. Other prescription medication within 7 days prior to the baseline visit or withinor 5 half-lives (whichever is longer) with the exception of the following whichare allowed: i. For the bipolar disorder group, prescribed psychotropic medications as long as theyare not included in the list of CYP2D6 and CYP2C19 medications listed in exclusion's 3and 4 below. ii. Limited use (not more than 3 days per week) medications (non CYP2D6 or CYP2C19substrates) such as prn treatments for asthma or acute migraine. iii. Women who are taking hormone replacement therapy or hormonal contraception mustbe on a stable regimen for 30 days prior to screening and remain on that regimenthroughout the study iv. Paracetamol may be used at doses of 1 g/day Herbal supplements must be discontinued 28 days prior to the first dose of studymedications. At the discretion of the investigator a shorter drug free ordiscontinuation period may be acceptable depending on the precise drugs/supplementstaken.
6. As JNJ-18038683 is a strong inhibitor of cytochrome P450 2D6, use of the followingCYP2D6 substrates will be an exclusion: carvedilol, S-metoprolol, propafenone,timolol, amitriptyline, clomipramine, desipramine, fluoxetine, imipramine, paroxetine,venlafaxine, haloperidol, perphenazine, risperidone, thioridazine, zuclopenthixol,alprenolol, amphetamine, aripiprazole, atomoxetine, bufuralol, chlorpheniramine,chlorpromazine, clonidine, codeine, debrisoquine, dexflenfluramine, dextromethorphan,donepezil, duloxetine, encainide, flecainide, fluvoxamine, lidocaine, metoclopramide,methoxyamphetamine, mexilletine, minaprine, nebivolol, nortriptyline, ondansetron,oxycodone, perhexiline, phenacetin, phenformin, promethazine, propafenone,propranolol, sparteine, tamoxifen, tramadol, venlafaxine. Participants planning to usethese medications after their participation in the study must commit to a two-weekwashout period at the end of the study before commencing these medications.
7. As JNJ-18038683 is a moderate inhibitor of cytochrome P450 2C19, use of the followingCYP2C19 substrates will be an exclusion: Proton pump inhibitors, phenytoin,phenobarbitone, diazepam, Norphenytoin, S-mephenytoin, phenobarbitone, amitriptyline,carisoprodol, citalopram, chloramphenicol, clomipramine, clopidogrel,cyclophosphamide, hexobarbital, imipramine, indomethacin, labetalol, R-mephobarbital,moclobemide, nelfinavir, nilutamide, primidone, progesterone, proguanil, propranolol,teniposide, warfarin, voriconazole. Participants planning to use these medicationsafter their participation in the study must commit to a two-week washout period at theend of the study before commencing these medications.
8. Currently taking medications with significant 5HT7 antagonist properties (eglurasidone, vortioxetine)
9. Treatment with another experimental medicine drug within the 3 months preceding thefirst dose of study medication, over the course of the study, and two weeks afterdiscontinuing study medications
10. History of sensitivity to JNJ-18038683 or other medications with 5HT7 antagonistproperties.
11. History of febrile illness within 5 days prior to the first dose.
12. Any condition possibly affecting drug absorption (eg, gastrectomy).
13. 12-lead ECG considered abnormal by a clinician
14. A positive urine drug screen on or after the screening visit during their activeinvolvement in the study for opiates, methadone, cocaine, amphetamines (includingMDMA), barbiturates, benzodiazepines and cannabinoids.
15. Unwilling or unable to comply with the Lifestyle guidelines.
16. Participants who, in the opinion of the investigator, have any medical orpsychological condition or social circumstances which would impair their ability toparticipate reliably in the study, or who may increase the risk to themselves orothers by participating.
17. Diagnosis of alcohol or drug dependence in the year prior to recruitment or diagnosisof harmful use of alcohol or drugs within the previous 6 months.
18. Female participants of child bearing potential who are not using adequatecontraception as specified in above criteria for inclusion.
19. Female participants that are currently pregnant or are breast feeding.
20. A history of moderate to severe head injury or neurological conditions that may impaircognitive performance
21. Ineligibility to undergo MRI imaging, for example the presence of a cardiac pacemakeror other electronic device or ferromagnetic metal foreign bodies as assessed by astandard pre-MRI questionnaire.
22. Participant weight in excess of 126kg or physical dimensions such that the participantmay not fit in the MRI scanner.
23. A history of claustrophobia or participant feels unable to lie in a MRI scanner for aperiod of around one hour. Additional exclusion criteria for participants with bipolar disorder
24. Significant change in dose or type of prescribed psychotropic medications in the monthprior to the Screening visit or likely change during the study. Additional exclusion criteria for healthy participants
25. A personal history of any significant psychiatric disorder including a history ofsuicide attempts or significant suicidal ideation or a family history of severe mentalillness (such as psychosis, bipolar disorder or schizophrenia).