A Study to Investigate the Antidepressant Mechanism-of-action of JNJ-42847922 in Participants With Major Depressive Disorder

The HDRS17 is a Clinician-Administered rating scale designed to assess the severity of symptoms in participants diagnosed with depression with a total score range of 0 to 52. It is the most widely used symptom severity measure for depression. Each of the 17 items is rated by the clinician on either a 3- point (0 to 2) or a 5-point scale (0 to 4). The point scale uses a rating of 0 (absent), 1 (doubtful to mild), 2 (mild to moderate), 3 (moderate to severe), and 4 (very severe). Total score will be calculated by summing up the individual item score. The higher the score, the more severe the depression.

The HDRS17 is a Clinician-Administered rating scale designed to assess the severity of symptoms in participants diagnosed with depression with a score range of 0 to 52. It is the most widely used symptom severity measure for depression. Each of the 17 items is rated by the clinician on either a 3- point (0 to 2) or a 5-point scale (0 to 4). The point scale uses a rating of 0 (absent), 1 (doubtful to mild), 2 (mild to moderate), 3 (moderate to severe), and 4 (very severe). Higher scores indicate worsening. HDRS17 Sleep Item-Adjusted is derived from the HDRS17 scale excluding the 3 sleep items (4, 5, and 6) from the total score.

The HDRS17 anxiety/somatization factor derived from Cleary and Guy's factor analysis of the HDRS scale, includes six items from the original 17-item version: the items for psychic anxiety, somatic anxiety, gastrointestinal somatic symptoms, general somatic symptoms, hypochondriasis, and insight. Anxious depression is often defined as Major Depressive Disorder (MDD) with high levels of anxiety symptoms, as reflected in an anxiety/ somatization factor score greater than or equal to (>=) 7. The score ranges from 0 to 18, with higher scores indicating greater severity of symptoms.

The 6-Item Hamilton Depression Scale (HAMD-6), derived by the sum of HAMD-17 items (the six items in the HAM-D6 are: depressed mood, guilt feelings, work and interests, psychomotor retardation, psychic anxiety, and general somatics [tiredness and pains]), evaluates "core" symptoms of Major Depressive Disorder (MDD). Total subscale scores range from 0 (normal) to 22 (severe). The higher the score, the more severe the depression.

The QIDS-SR16 is a patient reported measure designed to assess the severity of depressive symptoms. The total score ranges from 0 to 27. Using a scale of severity of depression of none, mild, moderate, severe, and very severe, corresponding QIDS-SR16 total scores are none 1 to 5, mild 6 to 10, moderate 11 to 15, severe 16 to 20 and very severe 21 to 27.

Association between major depressive disorder (MDD) symptoms and signals of hyper-arousal (as measured by electro-encephalography [EEG], polysomnography, and/or measures of autonomic arousal - heart rate variability) will be assessed by means of correlation analysis and mixed effect models.

The SDMaT measures the time to pair abstract symbols with specific numbers. The test includes a coding key consisting of 9 abstract symbols, each paired with a number ranging from 1 to 9. Following the key, the participant is presented with randomly ordered symbols and is required to respond orally by naming the number or enter the number corresponding to each symbol as fast as possible using a keypad. The number of correct substitutions within 90 seconds is recorded by computerized cognitive test battery.

The WLRT used for the computerized test battery that measures person's ability to encode, consolidate, store, and retrieve verbal information and is a sensitive test of verbal learning and memory in a variety of disease states, including MDD. The memory test will include a list of 15 words presented aloud, one at a time, through the iPad. After the 15-word list is presented, the participant will be asked to verbally recall as many of the words as possible. The 15 word list and participant recall will be conducted 4 more times (total 5 times). After the 5th learning trial and recall, performance on the learning trials of the original word list and on the delayed recall will be considered as the primary scores. The computer tablet will record and score the participant's responses to the evaluation.

The computerized (Revere.D) version of the TMT-B is modeled after the paper-and-pencil version of the test. The TMT-B measures divided attention and executive function (tracking and sequencing). The participant is instructed to draw a line to connect a set of 25 consecutively numbered and lettered circles, alternating sequentially between numbers and letters (that is, 1 A 2 B). The participant is instructed to work as quickly as possible while still maintaining accuracy. The TMT-B has acceptable reliability; reliability coefficients have typically been reported as exceeding 0.65. The TMT-B is sensitive to cognitive decline associated with MDD.

The B&L VAS is made up of 16 pairs of alternative descriptors of mood and attention at either end. The Bond-Lader of a 10 cm line. Participants will rate their feelings at the time of assessment by indicating the point on the line which best represent their mood. Each item is scored by measuring the position relative to the left hand end of the line and levels of anxiety, sedation, and dysphoria are then calculated from the combined scores of selected items. The score ranges from 0 to 100, with a high score reflecting a high level of anxiety, sedation or dysphoria.

The POMS measures individuals' mood states. The POMS measures individuals' mood states. This is a validated scale to measure positive and negative mood states. The POMS contains 30 items and assesses six identified mood factors: Tension-Anxiety, Depression-Ejection, Anger- Hostility, Vigor-Activity, Fatigue-Inertia, and Confusion-Bewilderment. Scoring of the instrument provides a global score of 0 to 120 or individual domain scores. Lower scores indicate better mood state. The POMS brief form is a simple self-rating instrument.

Plasma concentration assessment will be done to characterize the pharmacokinetics (PK) of JNJ-42847922 and its metabolites.

Percent change from baseline in biomarker includes high-sensitivity (hs) C-reactive protein (CRP), interleukin(IL) 6, IL10, IL1b, tumor necrosis factor (TNF) alpha, cortisol, growth hormone, adiponectin, leptin, brain-derived neurotrophic factor (BDNF), Insulin-like growth factor 1 (IGF1), interleukin-6 receptor (IL6R), insulin, glucose, adrenocorticotropic hormone, Kynurenine metabolites will be assessed.

An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.