Introduction
Depression is a prevalent health problem, often associated with comorbidities and poor health outcomes, such as decreased life expectancy [1]. Depressive disorders impose an average cost of US$ 7,638 on healthcare systems per person every year [5]. Therefore, it is crucial to consider preventive and therapeutic actions, such as environmental activities to improve the community’s physical and mental health while reducing medication use and decreasing the cost imposed on healthcare systems [6]. 
The nature-based therapeutic interventions involve plants and natural settings, such as tending to a garden for human health and well-being. These interventions are referred to by different terms, such as horticultural therapy, social and therapeutic horticulture, and people-plant relationships [7]. Previous studies have confirmed the positive effects of horticulture on physical health, mental health, emotional well-being, social functioning, anxiety, and depression [13-24]. 
To the best of our knowledge, there are inadequate RCTs regarding the effects of horticultural therapy on depression [13, 18], and most of them are limited to the elderly [14, 22] and recommended further analyses [23]. Therefore, this study, by assessing the effects of horticulture on depressed adults (not only the elderly), can fill the knowledge gap. This study aimed to determine the impact of indoor horticultural activities on mild-to-moderate depression symptoms. For this purpose, we hypothesized that the severity of depression symptoms in adults (18 years old or above) would differ between the experimental and control groups.

Methods
This research is a randomized controlled trial with two groups: (1) horticultural or experimental and (2) control groups. The statistical population included patients aged 19–66 years with mild-to-moderate depression symptoms, defined based on the Beck Depression Inventory (BDI-II) score. The computer-based randomization was performed through fourfold sampling blocks. 
After 334 candidates were screened for the eligibility criteria, 102 eligible participants were selected and assigned randomly to the experimental and control groups (51 members each). The sample size was calculated as 80 participants (40 members each). However, this study was a group research work with a long waiting time, and some randomized participants left the study before the intervention started (16 from the experimental group and 12 from the control group) (Figure 1), which was not predicted in advance.

Therefore, more participants were randomized to deal with this situation and prevent the loss of research efficiency. Moreover, we ensured the intervention would impose no risks or costs on participants. Then, the remaining participants were assigned to the experimental (35 participants) and the control (39 participants) groups. Both groups received educational worksheets as a non-pharmacological treatment. Moreover, the experimental group participated in weekly horticultural program sessions for six weeks. The horticultural program included indoor floriculture and vegetable gardening performed in groups. The severity of depression symptoms was appraised at baseline, after six weeks (at the end of intervention), and after ten weeks (four weeks after the end of intervention) through the BDI-II.

Results
Data analysis was conducted through the intention-to-treat (ITT) and complete-case methods. The statistical population included 96 participants. At baseline, 38 (39.6%) out of 96 participants had mild depression, whereas 58 (60.4%) had moderate depression. The independent t-test demonstrated no significant differences between the experimental and control groups regarding the mean age and BDI scores at baseline (Table 1).


In addition, the Chi-square test results indicated no significant differences in gender, educational attainment, and depression severity between the two groups at baseline. However, there was a significant difference between the two groups concerning occupational status. 
The repeated-measures ANOVA was used for data analysis by comparing changes in the BDI-II scores throughout the study, which showed lower scores among both groups at the end of the intervention and four weeks later as opposed to the baseline (Figure 2).

The results revealed that the mean BDI-II scores in the horticultural group declined by 5.68 (P=0.001) and 2.32 (P=0.016) points more than the control group at the end of the intervention and four weeks later, respectively.
After the end of the intervention and four weeks later, the experimental group indicated mean reductions of 9.90 (P<0.004) and 10.27 (P<0.033) in BDI-II scores based on the ITT analysis. Moreover, the repeated-measures analysis of variance for the BDI-II score indicated the significant effect of the intervention based on the ITT analysis (F=26.73, P=0.001) and the complete-case analysis (F=14.22, P=0.001) (Table 2). 



Discussion 
This study reported that indoor horticultural activities might mitigate the severity of depression symptoms. However, the efficiency of this method was reduced after the cessation of horticultural activities. Regarding the factors affecting the efficiency of horticultural activities, we found that horticultural activities were more effective in moderate depression symptoms than mild symptoms. Not only does this finding indicate the most suitable target population for this therapeutic activity, but it may also raise a question regarding potential differences between mild and moderate symptoms in psychopathology. Previous observations also confirm that pharmacological and psychiatric interventions have been effective in moderate to severe depression, but they have not had a significant effect on mild depression compared to the placebo [30]. The intervention might have boosted a sense of belonging through social connections in the experimental group. Behavioral activation might also have effectively mitigated depression symptoms, such as slowness, psychomotor agitation, decreased energy, and reduced interest in pleasurable behaviors, such as interpersonal relationships. The results of this study may serve as preliminary findings to support the potential role of horticultural programs in primary healthcare centers in collaboration with other community partners, such as local greenhouses, to help improve mental health conditions in people with mild-to-moderate depression. As this study was performed in groups, it appears that social communication affected the intervention outcomes. Therefore, it is recommended to conduct studies on people with depression symptoms to evaluate the effects of horticultural therapy per se. Finally, a more robust methodology is recommended with biomarker measurements and/or functional neuroimaging in future studies.

Ethical Considerations
Compliance with ethical guidelines
This study was approved by the ethics committee of Iran University of Medical Sciences (Code: IR.IUMS.REC.1397.54) and was registered by Iranian Registry of Clinical Trials (ID: IRCT20181206041871N1)

Funding
This study was extracted from the PhD thesis of France Minagar and was funded by Preventive Medicine and Population Health Research Center of Iran University of Medical Sciences.

Authors contributions
Conceptualization: France Minagar, Masoud Ahmadzad-Asl, Arash Tehrani Bani Hashemi, Batool Tayefi and Mozhdeh Ramezani; Investigation: France Minagar and Nassim Mohabbat; Project management and Supervision: France Minagar, Masoud Ahmadzad-Asl and Mozhdeh Ramezani; Initial draft preparation: France Minagar; Methodology: Arash Tehrani Bani Hash-emi and Mozhdeh Ramezani; Design, Methodology, software, data curation, data analysis, val-idation, funding acquisition: Mozhdeh Ramezani; Writing, review & editing: All authors.

Conflicts of interest
The authors declared that they had no conflict of interest. 

Acknowledgements
The authors would like to thank the manages of Flower and Plant Education Center of Al-Mahdi Park in Tehran and Ms. 

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