Change from baseline in MADRS total score up to Week 6 were reported. MADRS was a clinician-rated scale designed to measure depression severity and detect changes due to antidepressant (AD) treatment. The MADRS evaluated reported sadness, apparent sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. The scale consisted of 10 items, each of which was scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms),with higher score indicating a more severe condition. The MADRS total score was the sum of scores from individual question items and it ranged from 0 to 60, with higher scores indicated more severe conditions. Negative change in MADRS total score indicated improvement.

Full analysis set (FAS) included all randomized participants who received at least 1 dose of study intervention and had both the baseline and at least 1 postbaseline MADRS measurement.

Change from baseline in SHAPS total score up to Week 6 were reported. The SHAPS was a reliable, valid, and unidimensional instrument used to assess hedonic capacity in adults with Major Depressive Disorder. It is a 14-item, self-report tool with a completion time below 5 minutes. Each of the items had a set of 4 response categories: 1 = definitely agree/strongly agree, 2 = agree, 3 = disagree, and 4 = strongly disagree. The SHAPS total score was the sum of the 14 item scores, which ranged from 14 to 56. A higher SHAPS total score indicated higher levels of current anhedonia. Negative changes in the SHAPS total score indicated improvement.

FAS included all randomized participants who received at least 1 dose of study intervention and had both the baseline and at least 1 postbaseline MADRS measurement. Here, 'N' (overall number of participants analyzed) signifies number of participants evaluable for this outcome measure.

Genetic subgroup analysis included participants with bipolar depression and who were with P2RX7 Gain of Function single nucleotide polymorphism (P2RX7 GoF SNP) mutation genotype: heterozygous or homozygous. MADRS was a clinician-rated scale designed to measure depression severity and detect changes due to AD treatment. The MADRS evaluated reported sadness, apparent sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. The scale consisted of 10 items, each of which was scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms),with higher score indicating a more severe condition. The MADRS total score was the sum of scores from individual question items and it ranged from 0 to 60, with higher scores indicated more severe conditions. Negative change in MADRS total score indicated improvement.

FAS included all randomized participants who received at least 1 dose of study intervention and had both the baseline and at least 1 postbaseline MADRS measurement. Here, 'N' (overall number of participants analyzed) signifies number of participants evaluable for this outcome measure. Here, 'n' (number analyzed) is defined as participants analyzed at specified categories.

Change from baseline in MADRS total score up to Week 6 (Diagnosis Subgroup Analysis) were reported. Diagnosis subgroup analysis included participants with bipolar type 1 or II. MADRS was a clinician-rated scale designed to measure depression severity and detect changes due to AD treatment. The MADRS evaluated reported sadness, apparent sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. The scale consisted of 10 items, each of which was scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms),with higher score indicating a more severe condition. The MADRS total score was the sum of scores from individual question items and it ranged from 0 to 60, with higher scores indicated more severe conditions. Negative change in MADRS total score indicated improvement.

FAS included all randomized participants who received at least 1 dose of study intervention and had both the baseline and at least 1 postbaseline MADRS measurement. Here, 'N' (overall number of participants analyzed) signifies number of participants evaluable for this outcome measure. Here, 'n' (number analyzed) is defined as participants analyzed at specified categories.

Biomarker subgroup analysis included specific (3-Marker Model [3MM]) biomarker profile: Yes or No. 3MM biomarker profile was defined as serum C-reactive protein >3 mg/Liter(L) and soluble interleukin-6 receptor >25 micrograms(mcg)/L or tumor necrosis factor >4 nanograms(ng)/L at baseline. MADRS was a clinician-rated scale designed to measure depression severity and detect changes due to AD treatment. MADRS evaluated reported sadness, apparent sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. Scale consist of 10 items each of which was scored from 0(item not present or normal) to 6(severe or continuous presence of the symptoms),with higher score indicating a more severe condition. MADRS total score was sum of scores from individual question items, ranged from 0 to 60,with higher scores indicated more severe conditions. Negative change in MADRS total score indicated improvement.

FAS included all randomized participants who received at least 1 dose of study intervention and had both the baseline and at least 1 postbaseline MADRS measurement. Here, 'N' (overall number of participants analyzed) signifies number of participants evaluable for this outcome measure. Here, 'n' (number analyzed) is defined as participants analyzed at specified categories.

Vital signs parameters included pulse rate (abnormally low [AL]: <50 beats per minute [bpm] and with >15 bpm decrease from baseline and abnormally high [AH]: >100 bpm and with >15 bpm increase from baseline), Systolic blood pressure (SBP) (AL: <90 millimeters of mercury [mmHg] and with >20 mmHg decrease from baseline and AH: >180 mmHg and with >20 mmHg increase from baseline), Diastolic blood pressure (DBP) (AL: <50 mmHg and with >15 mmHg decrease from baseline and AH: >105 mmHg and with >15 mmHg increase from baseline) , temperature (AL:<35.5 and AH:>37.5 degree Celsius [C]), respiratory rate (AH :>20 breaths per minute), and weight (AL: decrease from baseline >7% and AH: increase from baseline >7%). Weight was planned to analyzed at Weeks 6 and 8 only. Treatment-emergent concluded if postbaseline value was above/below upper/lower limit and baseline value was below/above the upper/lower limit.

Safety analysis set included all randomized participants who took at least 1 dose of study intervention. Here, 'N' (overall number of participants analyzed) signifies number of participants evaluable for this outcome measure. Here, 'n' (number analyzed) is defined as participants analyzed at specified categories.

Change from baseline in clinical laboratory values in male hormone (Inhibin B) were reported.

Safety analysis set included all randomized participants who took at least 1 dose of study intervention. Here, 'N' (overall number of participants analyzed) signifies number of participants evaluable for this outcome measure. Here, 'n' (number analyzed) is defined as participants analyzed at specified timepoints.

Change from baseline in clinical laboratory values in male hormone (luteinizing hormone) were reported.

Safety analysis set included all randomized participants who took at least 1 dose of study intervention. Here, 'N' (overall number of participants analyzed) signifies number of participants evaluable for this outcome measure. Here, 'n' (number analyzed) is defined as participants analyzed at specified timepoints.

Change from baseline in clinical laboratory values in male hormone (prolactin) were reported.

Safety analysis set included all randomized participants who took at least 1 dose of study intervention. Here, 'N' (overall number of participants analyzed) signifies number of participants evaluable for this outcome measure. Here, 'n' (number analyzed) is defined as participants analyzed at specified timepoints.

Change from baseline in clinical laboratory values in male hormones (sex hormone binding globulin, testosterone [free], testosterone [high sensitivity], and testosterone [low sensitivity]) were reported.

Safety analysis set included all randomized participants who took at least 1 dose of study intervention. Here, 'N' (overall number of participants analyzed) signifies number of participants evaluable for this outcome measure. Here, 'n' (number analyzed) is defined as participants analyzed at specified categories.

Number of participants with abnormal laboratory values: serum chemistry were reported. It included: aspartate aminotransferase (high), alanine aminotransferase (high), bilirubin (high/low), and alkaline phosphatase (high/low). Only categories with data were reported.

Safety analysis set included all randomized participants who took at least 1 dose of study intervention. Here, 'n' (number analyzed) is defined as participants analyzed at specified categories.

Number of participants with clinically significant abnormal laboratory values: hematology were reported.

Safety analysis set included all randomized participants who took at least 1 dose of study intervention.

Number of participants with clinically significant abnormal laboratory values: urinalysis were reported.

Safety analysis set included all randomized participants who took at least 1 dose of study intervention.

Number of participants with TEAEs were reported. An adverse event (AE) is any untoward medical occurrence in a clinical study participants who administered a medicinal (investigational or non-investigational) product and does not necessarily have a causal relationship with the treatment. A TEAE defined as an AE that occurred at or after the first dose administration up to day of the last dose plus 30 days.

Safety analysis set included all randomized participants who took at least 1 dose of study intervention.

Number of participants with treatment-emergent abnormalities in ECGs were reported. It included ECG mean heart rate (abnormally low [AL]: <50 and abnormally high [AH]: >100 beats per minute [bpm]), PR Interval (AL: <120 and AH: >200 milliseconds [msec]), QRS Duration (AL: <60 and AH: >120 msec), and QT Interval (AL: <200 and AH: >500 msec). A treatment-emergent abnormalities in ECGs are defined as those abnormalities that occurred at or after the first dose administration.

Safety analysis set included all randomized participants who took at least 1 dose of study intervention. Here, 'n' (number analyzed) is defined as participants analyzed at specified categories.

Change from baseline in YMRS total score were reported. The YMRS was designed to measure the severity of manic symptoms, to gauge the effect of treatment on mania severity, and to detect a return of manic symptoms (for example relapse or recurrence). YMRS had 11 items : 4 items (irritability, speech, thought content, and disruptive/aggressive behavior) were graded on a scale of 0 to 8 and the remaining 7 items (elevated mood, increased motor activity, sexual interest, sleep, language-thought disorder, appearance, and insight) were graded on a scale of 0 to 4. Higher scores indicated greater symptom severity. Responses were summed to yield YMRS total score ranged from 0 to 60 , with higher scores reflecting greater severity of mania.

Safety analysis set included all randomized participants who took at least 1 dose of study intervention. Here, 'N' (overall number of participants analyzed) signifies number of participants evaluable for this outcome measure.

C-SSRS is a clinician-rated instrument that reports severity of both suicidal ideation (SI) and suicidal behavior (SB). SI categories: 1 (wish to be dead), 2 (nonspecific active suicidal thoughts), 3 (active suicidal ideation with any methods [not plan] without intent to act), 4 (active SI with some intent to act, without specific plan), and 5 (active SI with specific plan and intent). SB categories: 6 (preparatory acts or behavior), 7 (aborted attempt), 8 (interrupted attempt), 9 (actual attempt), and 10 (suicide). An additional category for non-suicide: non-suicidal self-injurious behavior. SI/SB was indicated by a "yes" answer to any of the listed categories. Score of 0 (no SI or SB) was assigned. Maximum score of 1 to 10 was assigned if suicidal ideation or behavior was present. Scoring was grouped into 3 categories: No SI/SB (0), SI (score 1 to 5), and SB (score 6 to 10), with higher scores indicating more severe ideation/behavior.

Safety analysis set included all randomized participants who took at least 1 dose of study intervention. Here, 'N' (overall number of participants analyzed) signifies number of participants evaluable for this outcome measure.

Change from baseline in CGI-S score were reported. The CGI-S provides an overall clinician-determined summary measure of the severity of the participant's illness that takes into account all available information, including knowledge of the participant's history, psychosocial circumstances, symptoms, behavior, and the impact of the symptoms on the participant's ability to function. The CGI-S is a 7-point global assessment scale that measures the clinician's impression of the severity of mental illness exhibited by a participant, and rated on a scale of 1 to 7: 1=normal (not at all ill); 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; and 7=among the most extremely ill participants. Higher scores indicate worsening. Negative change in CGI-S score indicate improvement.

Safety analysis set included all randomized participants who took at least 1 dose of study intervention. Here, 'N' (overall number of participants analyzed) signifies number of participants evaluable for this outcome measure.

Plasma concentrations of JNJ-55308942 were reported.

Pharmacokinetics (PK) analysis set included all participants who received at least 1 dose of JNJ-55308942 and had at least 1 valid blood sample drawn for PK analysis. Here, 'n' (number analyzed) is defined as participants analyzed at specified categories. Data for this outcome measure was not planned to be collected and analyzed for placebo arm.

Change from baseline in PROMIS score - ability to participate in social roles and activities T-Scores were reported. The PROMIS - APS item bank assessed the perceived ability to perform one's usual social roles and activities. The item bank did not use a time frame (for example, over the past seven days) when assessing the APS. The Short Form 4a included 4 items that represent this concept. Each question had 5 response options ranging in value from 1 to 5 with higher scores indicating better social function. The total raw score for the short form was calculated by summing the values of the response to each question, so for the 4-item form, the lowest possible raw score was 4; the highest possible raw score was 20. The total raw score was converted to a T score with a mean of 50 and a standard deviation of 10. Higher T-scores indicate better social function.

FAS included all randomized participants who received at least 1 dose of study intervention and had both the baseline and at least 1 postbaseline MADRS measurement. Here, 'n' (number analyzed) is defined as participants analyzed at specified categories.

Change from baseline in PHQ-9 total score were reported. PHQ-9 is 9-item, self-report scale assessed depressive symptoms. Each item was rated on 4-point scale (0=Not at all, 1=several days, 2=more than half days, 3=nearly every day. The participant's item responses were summed to provide PHQ-9 total score (range of 0 to 27) with higher scores indicating greater severity of depressive symptoms.

FAS included all randomized participants who received at least 1 dose of study intervention and had both the baseline and at least 1 postbaseline MADRS measurement. Here, 'n' (number analyzed) is defined as participants analyzed at specified categories.

Change from baseline in GAD-7 total score were reported. GAD-7 is a brief and validated 7-item self-reported questionnaire for assessment of overall GAD. Participants responded to each item using a 4-point scale with response categories of 0=not at all, 1=several days, 2=more than half the days, and 3=nearly every day, with a higher score representing a more severe condition. Item responses were summed to yield GAD-7 total score which ranged of 0 to 21, where higher scores indicated more anxiety.

FAS included all randomized participants who received at least 1 dose of study intervention and had both the baseline and at least 1 postbaseline MADRS measurement. Here, 'n' (number analyzed) is defined as participants analyzed at specified categories.

Number of participants who achieved response at Week 6 were reported. Response was defined as greater than or equal to (>=)50% improvement in MADRS total score from baseline. MADRS was a clinician-rated scale designed to measure depression severity and detect changes due to AD treatment. The MADRS evaluated reported sadness, apparent sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. The scale consisted of 10 items, each of which was scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms),with higher score indicating a more severe condition. The MADRS total score was the sum of scores from individual question items and it ranged from 0 to 60, with higher scores indicated more severe conditions. Negative change in MADRS total score indicated improvement.

FAS included all randomized participants who received at least 1 dose of study intervention and have both the baseline and at least 1 postbaseline MADRS measurement.

Number of participants who achieved remission at Week 6 were reported. Remission was defined as MADRS total score <=12. MADRS was a clinician-rated scale designed to measure depression severity and detect changes due to AD treatment. The MADRS evaluated reported sadness, apparent sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. The scale consisted of 10 items, each of which was scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms),with higher score indicating a more severe condition. The MADRS total score was the sum of scores from individual question items and it ranged from 0 to 60, with higher scores indicated more severe conditions. Negative change in MADRS total score indicated improvement.

FAS included all randomized participants who received at least 1 dose of study intervention and have both the baseline and at least 1 postbaseline MADRS measurement.

Change from baseline in MADRS total score up to Week 6 (subgroup of participants with mRNA transcript levels) was planned to be reported. Subgroup included participants with mRNA transcript levels at baseline that exceeded the medium level for both P2RX7 and IL-1-beta. MADRS was a clinician-rated scale designed to measure depression severity and detect changes due to AD treatment. MADRS evaluated reported sadness, apparent sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. The scale consisted of 10 items, each of which was scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms),with higher score indicating a more severe condition. MADRS total score was the sum of scores from individual question items and it ranged from 0 to 60, with higher scores indicated more severe conditions. Negative change in MADRS total score indicated improvement.

FAS included all randomized participants who had received at least 1 dose of study intervention and have both the baseline and at least 1 postbaseline MADRS measurement.

Change from baseline in MADRS total score up to Week 6 (concomitant medication subgroup analysis) was reported. Concomitant medication subgroup analysis included subjects with BD not taking any mood stabilizer or antipsychotic, taking a mood stabilizer alone, taking antipsychotic alone, and taking a combination of mood stabilizer and an antipsychotic. MADRS measures depression severity, detects changes due to AD treatment. It consists of 10 items (evaluate apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, suicidal thoughts), scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), summed to total possible score of 0 to 60. Higher scores indicate more severe conditions. Negative change in score indicates improvement.

FAS included all randomized participants who had received at least 1 dose of study intervention and have both the baseline and at least 1 postbaseline MADRS measurement. Here, 'N' (overall number of participants analyzed) signifies number of participants evaluable for this outcome measure. Here, 'n' (number analyzed) is defined as participants analyzed at specified categories. n=0 signifies no participant was available for the analysis.