An Investigation of Early Life Stress and Depression: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for An Investigation of Early Life Stress and Depression (NCT01701258), a randomized phase 1 study. The primary outcome is Dopamine Active Transporter Binding Potential.

2. Clinical Question

3. Trial Design

This completed Phase 1 study, NCT01701258, is titled “An Investigation of Early Life Stress and Depression.” Mclean Hospital is listed as the sponsor. The registry describes a randomized, triple-masked, parallel design, with enrollment of 153. The study started in 2013-08 and reached primary completion in 2017-05.

The arm descriptions distinguish participants by both abuse history and depression history. Participants with a history of childhood sexual abuse and a current episode of major depression are identified as CSA/MDD. CSA/RES participants had a history of childhood sexual abuse but no current or past major depressive disorder. The MDD group had a current major depressive episode without a history of childhood sexual abuse, while the Control group had neither the abuse history nor a current or past major depressive episode.

Within each of these groups, the arm descriptions list amisulpride and placebo during the fMRI session. Amisulpride is described as a single low-dose 50mg pharmacological challenge; the placebo arms received placebo. The registry labels the study parallel and randomized, but does not report the allocation sequence or the people covered by triple masking. Further details about how the diagnostic groups were recruited or assigned are not reported in the registry record.

The registry lists 7 outcome measures and 0 analyses. Its primary outcome is dopamine active transporter binding potential, measured during a 1 hour PET scan in Session 3. The posted record does not provide a single primary-outcome comparison with estimates and uncertainty, so the design description cannot be paired with a clear numerical account of the primary result.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: In session 1, subjects had a diagnostic interview, a physical exam, provided a blood sample, and completed surveys, to determine eligibility. Those eligible were invited to participate in the other sessions. Participants did not need to complete all sessions. The order depended on facility availability and convenience for participants.

Only the first 6 of 13 groups are shown.

Assessment and Scheduling

Reasons for not completing this period:

Drug+fMRI (Session 2)

PET (Session 3)

EEG (Session 4)

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: Our baseline population are the 96 individuals that were eligible for the study after the screening visit. Not all participants that were eligible after the screening visit went on to participate in the other study sessions. Baseline data were collected for all eligible participants in each cohort during the assessment and scheduling period.

6. Primary Endpoint

The registry lists the primary outcome as Dopamine Active Transporter Binding Potential, measured over 1 hour PET scan (Session 3).

The registered primary endpoint is dopamine active transporter (DAT) binding potential, measured using 11C-altropane during positron emission tomography (PET). The registry defines the measure as nondisplaceable binding potential, or BPND: at equilibrium, the ratio of specifically bound radioligand to nondisplaceable radioligand in tissue. It is reported as a ratio, with the mean as the summary parameter and the standard error as the stated dispersion measure. Higher BPND scores indicate greater binding potential.

In general, a PET binding measure can serve as an indicator of radioligand binding at a target in the tissue being imaged. In this study, DAT binding potential was selected to investigate a dopamine-related pathway in the context of childhood sexual abuse and depression. The endpoint is not itself a direct measure of depression symptoms, reward behavior, or clinical benefit. Nor does a binding-potential value alone establish the mechanism behind a group difference.

The registry gives the timeframe as a 1 hour PET scan in Session 3. Although it specifies the measure and its interpretation, it does not report a result estimate, a confidence interval, or a single comparison for this outcome. The registry record says the primary outcome has several categories or time points and was not reduced to one comparison. Consequently, the endpoint can be described, but its observed between-group pattern and precision cannot be evaluated from the posted outcome information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry classifies the primary outcome as continuous and summarizes it using a mean with standard error. The following statistical explanations are general; they do not describe analyses confirmed to have been performed in this study unless the registry explicitly says so.

What does a mean represent?

For a continuous measurement, a mean describes the central value in a group by combining the observed values into an average. It can provide a compact description of a group’s DAT binding potential. A mean on its own does not show how widely individual measurements vary, whether groups differ reliably, or whether the difference is clinically or biologically important. Those questions require additional context, including the amount of uncertainty around the estimate and the comparison being made.

How should the standard error be read?

In general, a standard error describes uncertainty in an estimated statistic, such as a group mean. It is not the same as the spread of individual participant measurements. A smaller standard error generally indicates a more precise estimate of the mean, while a larger one indicates greater uncertainty. The registry names standard error as the dispersion measure for the primary outcome, but it does not post the relevant means or standard errors. Thus, no precision assessment for the primary outcome can be made from the registry record.

Why does the comparison matter?

A result is interpretable only in relation to a defined contrast. For example, comparing amisulpride with placebo within a particular group asks a different question from comparing CSA/MDD participants with Control participants. The first concerns randomized challenge assignment; the second concerns groups defined by their histories and diagnoses. A mean for each arm would not, by itself, establish which contrast is primary or how the analysis accounts for the study’s multiple groups and outcome categories. The registry does not post a single primary-outcome comparison that resolves this issue.

What does a confidence interval add?

Generally, a confidence interval gives a range of values compatible with an estimate under the specified statistical method. Its width communicates precision, while its position helps readers assess the direction and size of the estimated contrast. A confidence interval does not guarantee that the true value lies within the interval, and it does not by itself establish practical importance. No confidence interval for the primary outcome is reported in the registry record, so neither the range of plausible contrasts nor the precision of an estimate can be evaluated.

What do the planning assumptions mean?

The registry describes planning illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. These are assumptions for planning calculations, not a report of the trial’s design justification or its achieved statistical power. Sample-size illustrations are hypothetical planning quantities; they do not show that a study had a particular probability of detecting an effect after the study was completed. The trial’s own sample-size justification is not reported in the registry record.

In general, a normal approximation uses a simplified probability model to estimate uncertainty or plan a comparison. Whether it is appropriate depends on the measurement, design, and data. Equal allocation is an assumption in the planning illustration, but the registry does not provide enough detail to confirm that the actual study allocation followed that assumption in every comparison. No planning illustration should be treated as an observed outcome.

What can be inferred from a randomized, masked design?

Randomization is intended to make assigned groups comparable on average with respect to measured and unmeasured characteristics, subject to how the randomization is implemented and the data are analyzed. Masking is intended to reduce the influence of knowledge of assignment on relevant study procedures or assessments. These are general purposes, not proof that bias was eliminated. The registry identifies randomized allocation, triple masking, and a parallel model, but does not describe the allocation sequence, who was masked, or how missing observations were handled.

The record’s outcome list and analysis count do not provide inferential results for the primary measure. Without an estimate, uncertainty interval, and definition of the contrast, general statistical principles cannot recover what the study found. The most defensible interpretation is therefore limited to the registered measure, design, and stated hypotheses, alongside the absence of a posted primary-outcome comparison.

10. Multiplicity, Missing Data and Analysis Populations

The study lists 7 outcome measures, and its primary endpoint is described as having several categories or time points. The registry does not reduce that endpoint to a single comparison, and it lists 0 analyses. The analysis plan, including how multiple outcomes, categories, time points, or group contrasts were handled, is not reported in the registry record.

In general, multiplicity arises when several statistical comparisons are considered. The more comparisons examined, the greater the chance that at least one result may appear noteworthy by chance if no adjustment or other prespecified strategy is used. Statistical approaches to multiplicity can include adjustment of significance thresholds or a hierarchy of outcomes and comparisons. Which approach is appropriate depends on the scientific question and analysis plan. The registry does not state whether any such strategy was used, so it is not possible to determine how multiplicity was addressed or how it affects interpretation.

The registry record also does not report missing-data counts for the primary endpoint, reasons for missing measurements, or a method for handling missing observations. It does not describe the analysis population for the PET outcome or state whether analyses followed randomized assignment, included only participants with evaluable scans, or used another population definition. The listed enrollment and the safety-group at-risk counts do not answer those endpoint-specific questions.

These omissions matter because the observed analysis population and the handling of unavailable measurements can influence estimates and their precision. They also limit assessment of whether the primary-outcome analysis followed a prespecified plan. Without outcome-level data and analysis details, neither the direction of possible bias nor its magnitude can be determined. Further information about multiplicity, missing data, and analysis populations is not reported in the registry record.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports zero serious adverse events, zero other adverse events, and zero deaths in each listed safety group. For the “All Participants” group, 153 are listed as at risk for serious events and 153 for other events; both event counts and deaths are zero. The “All Baseline Participants” group lists 96 at risk for each event category, again with zero reported events and deaths.

The record also lists the Control, MDD, CSA/RES, and CSA/MDD groups and their amisulpride and placebo fMRI-session subgroups. Each listed group has zero serious events, zero other events, and zero deaths. The subgroup at-risk counts differ, and the safety groups include broad groups as well as subgroups. These counts overlap conceptually and must not be added to produce a new total.

In general, a zero count means that no event of that category was recorded for the corresponding registry group during the reported safety collection. It does not establish that the risk was zero, nor does it describe events outside the registry’s reporting scope. The registry does not list serious adverse-event terms or provide further detail about ascertainment, follow-up, or event timing. These safety counts should be interpreted separately from the unreported primary PET outcome.

12. What the Result Does, and Does Not, Mean

The record establishes that a randomized, triple-masked, parallel Phase 1 study investigated brain pathways in adult females with varying childhood sexual abuse and depression histories. It also identifies amisulpride and placebo as the randomized fMRI-session challenge conditions and DAT binding potential as the primary outcome. These registry entries describe the research question and design; they do not establish what the outcome showed.

The primary endpoint is biologically oriented. It measures a PET radioligand binding ratio that the registry interprets as DAT binding potential, with higher BPND indicating greater binding potential. The measure is relevant to the study’s stated interest in dopamine-related pathways. It is not a direct measure of depression severity, recovery, everyday functioning, or prevention of re-victimization. The registry’s broader aims do not turn this imaging endpoint into evidence for those outcomes.

The registry does not post a single primary-outcome comparison, group estimates, or uncertainty intervals. As a result, it cannot establish the direction, size, or precision of a difference in binding potential. The absence of a posted result should not be recast as a null result, and the study hypotheses should not be presented as findings. The study’s randomized design does not fill this reporting gap: randomization supports interpretation of a defined contrast, but the record must still report the relevant estimate and its uncertainty.

The registry reports no serious adverse events, other adverse events, or deaths in its listed safety groups. That is a description of the posted safety counts, not a complete characterization of all possible risks. It also does not answer the primary biological question. The record does not report enough information about analysis populations, missing data, multiplicity, or the statistical analysis plan to assess these aspects of the results.

Accordingly, the trial can be described as an investigation of imaging measures and a pharmacological challenge in groups defined by depression and childhood sexual abuse history. Its posted record does not permit a conclusion about whether amisulpride changed DAT binding potential, whether the history groups differed, or whether the stated biological hypotheses were supported.

13. Why This Trial Matters Statistically

This study raises a statistical challenge common to clinical research that combines randomized interventions with groups defined by clinical and life-history characteristics. A randomized amisulpride-versus-placebo contrast and a comparison between depression or abuse-history groups are not interchangeable. They address different questions and require clear definitions of the estimand, analysis population, and outcome contrast.

Its primary measure also requires careful interpretation. PET binding potential is a ratio used as an imaging measure of a biological target; it is not itself a patient-centered clinical outcome. Statistical evidence about such a measure needs to be paired with a clear explanation of what contrast was estimated, how precise it was, and how that result relates to the study’s stated hypotheses. A measurement can be relevant to a biological question without directly demonstrating a clinical effect.

The registry illustrates why outcome reporting matters as much as design labels. Randomization and masking describe important features of conduct, but readers also need results and analysis details to judge the evidence. Here the record lists 7 outcome measures and 0 analyses, and the primary outcome is not reduced to a single comparison. Without estimates and uncertainty, readers cannot assess effect size, precision, or whether the observed data align with the hypotheses.

The record’s safety groups also emphasize the need to read denominators in context. Broad groups and arm subgroups are reported separately, and their counts should not be combined. Zero reported events are informative as registry counts, but they do not replace full information about event collection and follow-up.

Statistically, the trial matters as an example of a complex design for which the biological rationale and randomized structure are clearer than the posted inferential results. The gap limits reproducibility and prevents an evidence-based appraisal of the primary endpoint from the registry record alone.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The main limitation for interpretation is that the registry does not report a single primary-outcome comparison. It provides no DAT binding-potential means, standard errors, confidence intervals, or test results. The primary outcome is described as involving several categories or time points, but the record does not specify a comparison that can be used to summarize its result. Consequently, the direction and precision of the primary outcome are unavailable.

The study includes groups defined by depression and childhood sexual abuse history as well as randomized amisulpride and placebo arms. The registry does not provide outcome estimates for these groups or explain which contrasts were primary. It also does not report the randomization sequence, the identities of those covered by triple masking, or how the multiple group and outcome comparisons were handled.

Information about the analysis population and missing PET data is not reported in the registry record. Without those details, it is not possible to assess whether outcome availability differed by group or assignment, or how missing measurements might affect the reported analysis. A sample-size justification and the trial’s statistical analysis plan are also not reported. Planning illustrations based on an observed effect are not a substitute for those design details or for observed outcome estimates.

The safety record reports zero serious adverse events, other adverse events, and deaths across its listed groups, but does not provide serious-event terms or additional ascertainment details. The safety categories should not be interpreted as a complete account of every possible event. These limitations apply to the registry record; they do not establish that additional analyses or information do not exist elsewhere.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: An Investigation of Early Life Stress and Depression — NCT01701258.
• Registry record last updated 2025-05-07; status last verified 2025-05.
• Results first posted 2018-05-18.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

NCT01701258 is a completed Phase 1 randomized, triple-masked, parallel study sponsored by Mclean Hospital. The registry lists enrollment of 153, a start date of 2013-08, and primary completion in 2017-05. It investigated adult females with differing histories of childhood sexual abuse and depression, with randomized amisulpride and placebo challenge arms during an fMRI session.

The primary outcome is dopamine active transporter binding potential measured with 11C-altropane PET during a 1 hour scan in Session 3. The registry describes the endpoint as mean BPND, with standard error, and states that higher BPND indicates greater binding potential. Although 7 outcome measures are listed, the record lists 0 analyses and does not reduce the primary outcome to a single comparison. Primary-outcome estimates and uncertainty are not reported in the registry record.

All listed safety groups report zero serious adverse events, zero other adverse events, and zero deaths. Further details about the statistical plan, missing outcome data, and analysis populations are not reported in the registry record.