Perceived learning difficulty associates with depressive symptoms and substance use among students of higher educational institutions in North Western Ethiopia: A cross sectional study.

BACKGROUND: The potential role of perceived learning difficulty on depressive symptoms and substance use in the context of student population was seldom studied. This study aimed to investigate the association of perceived learning difficulty with depressive symptoms and substance use among university students in northwest Ethiopia.
METHODS: A cross sectional study was conducted on 710 pre-engineering students. A locally validated version of Patient Health Questionnaire (PHQ-9) was used to assess depressive symptoms at a cut off 5-9 indicating mild depressive symptoms and at a cut off 10 for major depressive symptoms. Perceived difficulty in school work was assessed by items dealing about difficulties in areas of course work. The response alternatives of these items were 0 = not at all, 1 = not so much, 2 = quite much, 3 = very much. The types of substances that students had used in their life and in the last three months were assessed. Negative binomial regression and multinomial regressions were employed to investigate the predictors of number of substance use and depressive symptoms respectively.
RESULTS: The prevalence of depressive symptoms was 71.4% (Mild: 30% and Major 41.4%). About 24.6% of participants had the experience of using at least one substance. Increment in perceived difficulties in learning score was associated with more use of substances (aRRR = 1.03, 95% CI: 1.01-1.06), mild level depressive symptoms (aOR = 1.10, 95% CI: 1.04, 1.56 and major depressive symptoms (aOR = 1.19, 95% CI: 1.13, 1.26). Every increment in anxiety score was associated with increased risk of mild level of depressive symptoms (aOR = 1.09, 95% CI: 1.01, 1.17) and major depressive symptoms (aOR = 1.28, 95% CI: 1.18, 1.37). Being male (aRRR = 5.54, 95% CI: 3.28, 9.36), urban residence (aRRR = 2.46, 95% CI: 1.62, 3.72) and increment in number of life threatening events (aRRR = 1.143, 95% CI: 1.08, 1.22) were associated with increased risk of substance use.
CONCLUSION: Perceived difficulties in learning independently predicted increased depressive symptoms as well as substance use among participants.

Background of the study

Depression during adolescence is a serious public health challenge which is associated with suicide [1, 2] reduced memory, lack of concentration and poor planning [3, 4], sadness, loss of interest on common task, hopelessness and lack of sleep and appetite [5]. Depression adversely affects adolescents’ school and physical development [6]. Moreover, it is strongly associated with antisocial behaviours [7], substance use and anxiety [2] and poor social functioning [6]. Depressive disorders accounted for 40.5% of Disability Adjusted Life Years (DALYs) caused by mental and substance use disorders [8] posing high challenges especially on individuals at productive stage [9, 10]. Its estimated cost of lost productivity is 210 billion dollars per year in [11]. In Ethiopia, depression contributes about 6.5% of burden of diseases, which is the highest share of burden compared to other forms of mental disorders [12]. Its impact is even greater than the burden of disease contributed by Human Immuno-Virus (HIV), Tuberculosis (TB), or malaria.

The impact of depression among students of higher educational institutions may even be worse. Higher education students who are depressed may not be able to cope up with the academic and social activities. For example, previous studies depicted that children and adolescents with major depressive disorder performed less than those without depression in various cognitive domains [4]. University students who are depressed and unable to concentrate on their academics may ultimately drop out from the program or be dismissed.

Though depression is least diagnosed and least recognized among adolescents [13], it is a very common health problem among students in higher institutions in all parts of the world [14]. The prevalence of adolescent depression was 13.05% and 43.5% using Composite International Diagnostic Interview (CIDI) and the Beck Depression Inventory (BDI) respectively in a systematic review study [15]. The prevalence of adolescent depression in high income countries ranged from 17% in USA [16] according to the Patient Health Questionnaire–9 to 18.4% among females and 11.5% among males in Finland students [17] based on the Finnish version of BDI (Beck Depression Inventory). The prevalence was even higher among adolescents in Low and Middle Income countries (LMICs) ranging from 22% in India [18] to 36% in Kenya [19] at a Patient Health Questionnaire (PHQ-9) cut off 10.

In Ethiopia, the weighed prevalence of depression for the five studies, which had used Composite International Diagnostic Interview (CIDI), was 6.8% [20]. The Prevalence of depression among higher educational institutions of Ethiopia was about 41% of students in University of Gondar [21] using Symptom Reporting Questionnaire-20 (SRQ-20) at cut off 8; 32% in Addis Ababa University as assessed by Centre for Epidemiologic Studies- Depression Scale (CES-D) [22] and 32.2% in Ambo University using CESD [1].

Substance use among Ethiopian higher education institutions is considerably rising. For instance, a study in Axum University showed that 28.7 of students have lifetime khat chewing; 34.5% have been drinking alcohol and 9.5% of them smoking cigarette. Citing previous studies, these authors also mentioned that prevalence of substance use among students in Debre Markos town to be 14.1%. Likewise, a study in Addis Ababa University [2] showed that prevalence of drinking alcohol, chewing Khat and smoking among students was 31.4%, 14.1% and 8.7% respectively.

While depression and substance abuse are strongly associated [2, 23], they have also common risk factors. For example, poor academic performance [24], extreme poverty [25, 26] and social determinants such as school and family environment [24, 26] were common risk factors for both. Nevertheless, the potential role of perceived learning difficulty on depressive symptoms and substance use in the context of student population was not examined for future design of intervention strategies. We hypothesized that increased perceived learning difficulty would associate with increased depressive symptoms and increased use of substances controlling other potential confounders: anxiety, self-efficacy, social support, list of threatening events and academic performance. Thus, this study aimed to investigate the association of perceived learning difficulty with depressive symptoms and substance use controlling for the potential confounders.

Methods

Study setting

The study was conducted in three universities located in northwestern Ethiopia: namely Debre Markos University (DMU), Bahir Dar University (BDU) and Debre Tabor University (DTU). Both BDU and DTU are located around lake Tana where there is mass production of Khat through irrigation. Several sstudents who are mainly adolescents from different nations and nationalities of Ethiopia are placed in each academic year in these universities.

Though substance use was not a common practice of local people in the towns where these universities are located, some farmers have recently begun to produce khat for commercial purposes and this has increased its accessibility. As a result, chewing khat has become a common practice in these places especially, among students of higher institutions.

Study design

A cross-sectional quantitative study was done among pre-engineering students of selected universities. Data about the students’ socio-demographic variables, current status of depressive symptoms, substance use, anxiety, social support and experience of stressful life events were collected using survey questionnaire.

Target population

Freshman students of 2016/2017 academic year were the target population. Each university had about 3000 freshman students within the given academic year. That is more than 9000 freshman students were attending their education from three selected universities. Eligibility criteria for selecting participants included being freshman student and not having disability hearing to the extent of impairing informed consent.

Sampling techniques and sample size

We purposively selected Bahirdar University (BDU), Debre Markos University (DMU) and Debre Tabor University (DTU) all of which were found in northwestern Ethiopia. Each of these universities represented first, second and third generation universities respectively. These universities were purposively selected based on accessibility and availability of substances in the universities’ local areas. Among the student population, we purposively selected first year students in college of Technology for their high rate of attrition for another study. Thus, sample size was estimated for another study using single proportion formula with design effect of 1.5 and non-response rate of 10%. Accordingly, a total of 710 participants were required. Cluster sampling was used to recruit participants from the pre-engineering students (379 from DMU, 172 from DTU and 159 from BDU) where sections were units of clustering.

Assessment

The outcome variable was depressive symptoms as assessed by using a locally validated version of PHQ-9. It has very good sensitivity and specificity to diagnose depressive symptoms and its severity forms at different cut offs: a score of five or more to indicate mild depressive symptoms and at a cut off 10 or more for major depressive symptoms [27]. Substance use was assessed by using a composite scale taken from previous study [22]. The ten items of the scale asked the life time and the three months experience of using five substances: khat, alcohol, tobacco, shisha and depressants [22]. The options were never (0), monthly (1), weekly (2) and daily (3). The instrument has internal consistency of 89%. A range of predictor variables were used in the study: Anxiety was assessed by Generalized Anxiety disorder scale (GAD) [25]; Perceived social support was assessed by OSSLO social support scale with three items [28]; Self-efficacy was assessed using a 10 item General Self-Efficacy Scale [29] and List of threatening events was assessed by a 12 dichotomous items asking whether students experienced the events in the last 12 months [21]. Perceived difficulty in school work was assessed by items taken from previous studies [17] that requests participants whether they had difficulties in areas of school work such as paying attention to teaching, teamwork, getting along with peers, getting along with teachers, doing homework, preparing for examinations, finding personal learning strategies, doing activities requiring initiative, doing reading tasks and doing writing tasks. The response alternatives were 0 = not at all, 1 = not so much, 2 = quite much, 3 = very much. Socio-demographic data such as participants’ gender, age, residence and religion were collected. We compiled the data collection tools in a form of self-administered Amharic version of questionnaires which took an average of 20 minutes to complete.

Data analysis

Statistical Packages for Social Sciences (SPSS) version 20 was used to conduct data analysis. Descriptive statistics was used to investigate prevalence of substance use and depressive symptoms. Negative binomial regression and multinomial regressions were employed to investigate the predictors of number of substance use and depressive symptoms respectively. Complete case analysis was used to treat missing data. STROBE Checklist [30] was used to ensure reporting of all relevant items for cross-sectional studies.

Ethics approval and consent to participate

Ethical clearance was obtained from Ethics committee of Institute of Educational and Behavioral Sciences, Debre Markos University. Written consent was obtained from study participants and that was approved by the ethics committee. Participants were told about the objectives of the study and we informed them that they have the right to withdraw from the study or not to respond to any of the questions they didn’t want to respond.

Results

A total of 703 participants completed questionnaires out of 710 questionnaires with a response rate of 99%. But, 56 participants (9%) had missing data in either of the predictors and were excluded from analysis leaving 647 (91%) participants for multivariable regression analysis (Fig 1). The demographic background of the participants is indicated in Table 1. Mean age of participants was 19.91 years. More than two third of the participants were males; and most (60.5%) of them were residing in urban areas. The majorities (87.5%) of them were orthodox Christianity followers and about 6.4% of the participants had chronic illnesses.

Fig 1

Participant flow diagram.

Table 1

Characteristics of the participants.

Characteristics		Count	%
Sex	Male	475	67.6
	Female	193	27.5
Residence	Urban	425	60.5
	Rural	267	38.0
Religion	orthodox	615	87.5
	Muslim	30	4.3
	protestant	35	5.0
	Others	9	1.3
Chronic illness	Yes	45	6.4
	No	653	92.9

Age (Mean = 19.91, minimum = 18, Maximum = 37, standard deviation = 1.48)

PHQ-9 total score (Mean = 9.09; Maximum = 27; Minimum = 0; standard deviation = 6.58)

As indicated in Table 2, the prevalence of mild level of depressive symptoms was about 30% and that of major depressive symptoms was about 41.4% which was statistically similar among both males and females (Mean PHQ-9 score = 9.09 and standard deviation = 6.58). Generally about 70% of participants had a PHQ-9 score of five or more indicating probable depressive symptoms. Loss of interest on common tasks was the most frequent symptom among the participants (mean score = 1.61) followed by getting weak (mean score = 1.22) and hopelessness (mean score = 1.21).

Table 2

Prevalence of depressive symptoms.

Variables		Nill	Mild	Major	At least Mild
Sex	Males	140 (29.5%)	141 (29.7%)	194 (40.8%)	335 (70.5%)
	Females	52(26.9%)	63 (32.6%)	78 (40.4%)	141 (74.1%)
Residence	Urban	128 (30.1%)	136 (32.0%)	161 (37.9%)	297 (69.9%)
	Rural	69 (25.8%)	73 (27.3%)	125 (46.8%)	198 (74.2%)
University	DMU	124 (32.7%)	98 (25.9%)	157 (41.4%)	255 (67.3%)
	DTU	39 (22.7%)	60 (34.9%)	73 (42.4%)	133 (77.3%)
	BDU	38 (25.0%)	53 (34.9%)	61 (40.1%)	114 (75.0%)
	Total	201 (28.6%)	211 (30.0%)	291 (41.4%)	502 (71.4%)

DMU: Debre Markos University; DTU: Debre Tabor University; BDU: Bahir Dar University.

Table 3 shows the three months prevalence of substance use. About one-fourth (24.6%) and nearly one-third (29.6%) of the participants had experience of using at least any one of the substance listed in Table 3 during the last three months and in lifetime respectively. Among the different forms of substances, alcohol was the most commonly (23.6% and 27.5%) used substance during the last three months and in lifetime respectively.

Table 3

Last three months and lifetime prevalence of substance use.

	Three months		Lifetime
Substance	Never	At least once	Never	At least once
Khat use in last 3 months	675 (96.8)	22 (3.2)	653 (94.0)	42 (6.0)
Shisha- use in last 3 months	681 (97.7)	16 (2.3)	673 (97.0)	21 (3.0)
Alcohol- use in last 3 months	531 (75.4)	166 (23.6)	498 (72.1)	193 (27.5)
Tobacco- use in last 3 months	672 (95.4)	25 (3.6)	666 (96.1)	27 (3.9)
Depressant—use in last 3 months	682 (97.8)	15 (2.2)	679 (97.7)	16 (2.3)
Experience of using either of the substances	525(75.4)	172 (24.6)	481 (70.4)	199 (29.6)

In negative binomial regression (Table 4), each increment in perceived difficulties in learning score was associated with increased risk of using more and more numbers of substances (aRRR = 1.03, 95% CI: 1.01, 1.05). There was more than four times increased risk of experiencing increased number of substances among males compared to females (aRRR = 4.44, 95% CI: 2.99, 6.58). With respect to residence, there was more than two times increased risk of experiencing greater number of substances use among urban residents (aRRR = 2.21, 95% CI: 1.65, 3.00) compared to rural residents. On the other hand each increment in PHQ-9 score (aRRR = 1.03, 95% CI: 1.01, 1.06) and number of life threatening events (aRR = 1.14, 95% CI: 1.08, 1.22) were associated with and increased risk of experiencing greater number of substances.

Table 4

Predictors of increased number of substance use in last 3 months in negative binomial regression model.

Parameter	95% Wald Confidence Interval for RRR
	RRR	Lower	Upper
Gender: Males	4.435**	2.990	6.577
Females	1	1	1
Residence: Urban	2.207**	1.649	2.955
Rural	1	1	1
University: DMU	.884	0.624	1.251
DTU	1.055	0.730	1.525
BDU	1	1	1
Having chronic illness: Yes	2.541**	1.679	3.846
No	1	1	1
Anxiety Score	.988	.956	1.021
Self-Efficacy score	0.978*	0.959	0.998
Perceived difficulties in learning	1.032**	1.011	1.053
Social support	0.982	0.945	1.022
PHQ-9 score	1.033*	1.010	1.057
Life threatening events	1.143**	1.076	1.215

** p-value less than 0.005

* p-value less than 0.05.

DMU: Debre Markos University; DTU: Debre Tabor University; BDU: Bahir Dar University.

In a multinomial regression model aimed to investigate predictors of depressive symptoms (Table 5), each increment in perceived difficulties in learning score was associated with increased risk of having mild depressive symptoms (aOR = 1.10, 95% CI: 1.04, 1.16) and major depressive symptoms (aROR = 1.19, 95% CI: 1.13, 1.26).

Table 5

Predictors of depression in multinomial regression model.

Variables	Mild depressive symptoms	Major depressive symptoms
	RRR (95%)	RRR
Gender: Male	0.735 (0.409, 1.324)	0.745 (0.396, 1.405)
Female	1	1
Residence: Urban	0.452* (0.249, 0.820)	0.353** (0.187, 0.664)
Rural	1	1
University: DMU	0.400*(0.165, 0.698)	0.340* (0.165, 0.698)
DTU	0.827 (0.409, 2.135)	0.934 (0.409, 2.135)
BDU	1	1
Anxiety score	1.088* (1.014, 1.168)	1.276** (1.184, 1.374)
Self-efficacy score	1.008 (0.966, 1.053)	0.967 (0.925, 1.010)
Perceived learning difficulties	1.099**(1.044, 1.157)	1.191** (1.129, 1.257)
Social support score	0.935 (0.854, 1.024)	0.910 (0.826, 1.002)
Semester GPA	0.774 (0.460, 1.301)	0.682 (0.391, 1.190)
Number of substance	1.341 (0.889, 2.022)	1.551 (1.021, 2.355)
Chronic illness: Yes	0.545	1.248 (0.357, 4.365)
No	1	1

DMU: Debre Markos University; DTU: Debre Tabor University; BDU: Bahir Dar University.

Every increment in anxiety score was associated with 8.8% increased odds of mild level of depressive symptoms (aOR = 1.09, 95% CI: 1.01, 1.17) and 28% increased odds of major depressive symptoms (aOR = 1.28, 95% CI: 1.18, 1.37). Each increment in number of substance used by students was also associated with about 55% increment in odds of major depressive symptoms (aOR = 1.55, 95% CI: 1.02, 2.36). Being urban resident and Debre Markos University student were associated with reduced odds of both mild (aOR = 0.40, 95% CI: 0.16, 0.70) and major levels of depressive symptoms (aOR = 0.34, 95% CI: 0.16, 0.70).

Discussion

About 70% of participants had a PHQ-9 score of five or more indicating probable depressive symptoms (mild level of depressive symptoms is about 30% and that of 40% major depressive symptoms) which was statistically similar among both males and females. Loss of interest on common tasks, getting weak and sad mood were the most common depressive symptoms among the participants. Perceived learning difficulty was independently associated with increased risk of having depressive symptoms and increased risk of using different substances. This finding supports previous studies where low educational success was an antecedent to different risk behaviors including substance use as underlined in Social control theory [31]. This study has identified potential area of intervention, perceived difficulties in learning that can play a double role of improving both depressive symptoms and substance use at the same time. The positive association between perception of learning difficulties and use of substances may be explained by the students’ use of psychoactive substances like khat for study purposes and the accessibility of khat in the study areas.

The prevalence of depressive symptoms varies across settings depending on cut offs and sample population. The prevalence of depressive symptoms in our samples is very high compared to the population study in southern Ethiopia which reported about 12% of depressive symptoms using the same measure [32]. But, the finding is comparable with a 43.5% prevalence of depressive symptoms using Beck depressive symptoms Inventory (BDI) in a Meta-analysis of about 53 international studies [15]. A 27.7% prevalence of depressive symptoms in Qaboos University using PHQ-9 diagnostic criteria at a cut point of more than 11 [33] was also comparable to our finding of 40% prevalence at cut off 10 using the same measure. Our finding supports a 41% prevalence of mental distress among students in University of Gondar [1, 21] and 32% prevalence of depressive symptoms in AAU as assessed by CEDS [22] and 32.2% in Ambo University using CESD [1].

Every increment in anxiety score and increased use of substances were associated with increased risk of having depressive symptoms. Anxiety arising from the challenges of adapting the new university environment among the rural freshman students may explain their increased risk of depressive symptoms and increased use of substances.

Alcohol is the most commonly used substance and nearly one fourth and one third of the participants used at least one of the substances in the last three months and in their lifetime respectively. In the same way, previous studies [34] in Europe found that substance use specially, alcohol, was the highest among adolescents. This is because of most easily accessibility of alcohol is the study area. Indeed, the current finding is somewhat similar to previous studies [35] which states that easy availability of substances increases use of substances. Likewise, a study conducted in Spain on adolescents [34] showed that there is high rate of substance use.

Previous studies, conducted on prevalence of substance use among students in Debre Markos town found it to be 14.1% [36]. Meanwhile research done in other higher institutions of Ethiopia showed that students are at risk of substance use. For instance, a study in Axum University showed that 28.7% of students have lifetime khat chewing; 34.5% have been drinking alcohol and 9.5% of them smoke cigarette.

The low prevalence of substance use in Debre Markos university can be explained by the relatively low availability of substances in the area and the cultural values of the community compared to Bahir Dar and Debre Tabor. In line with the effect of cultural, familial and environmental factors for substance use, empirical literature suggests that risk factors for drug abuse include having parents or siblings with problem of drug use, as well as family disruption, and poor attachment. The limitation of this study was that the time of data collection was nearer to final exam of the students. This might have inflated the prevalence of depressive symptoms. The assessment tool we used for substances use was a composite measure and was not validated to assess the severity of the problem. Besides, a high rate of missing data in the predictors might have affected our results.

Conclusion

Perceived difficulties in learning independently predicted increased depressive symptoms as well as substance use among adolescents.

(SAV)

Click here for additional data file.

20 Aug 2020

PONE-D-20-08001

Perceived learning difficulty associates with depressive symptoms and substance use among students of higher educational institutions in North Western Ethiopia: A cross sectional study

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I could not get a comment from the Second reviewer unfortunately. But I think that the authors should address the methodological points the first reviewer pointed out.

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Reviewer #1: The authors aimed to investigate the prevalence and risk factors of depressive symptoms and substance use among university students in North-Western Ethiopia. Focusing on depression and substance use is quite significant both from a clinical and public health perspective. However, several points should be critically considered.

[Major comments]

The authors assert the importance of clinical depression and substance abuse; however, this cross-sectional study assesses the level of depressive symptoms and substance use that compromise with a flaw, limiting the clinical relevance which needs to be considered.

The authors report that the prevalence of mild levels of depressive symptoms to be about 30%, and that of major depressive symptoms to be about 40%. However, the mean (SD) PHQ-9 score of the sample is not given, which makes it ambiguous whether the sample has marked depression symptoms that may cause noticeable problems in relationships with others and day-to-day school activities (functional impairment). The mean (SD) PHQ-9 score of the sample should be provided. The authors also report “mild” and “major” depressive symptoms based on PHQ-9; however, the score range of mild and major depressive symptoms category is not given.

The authors also report that substance use was assessed by a composite scale the asking the lifetime and the three months experience of using five substances: khat, alcohol, tobacco, shisha, and depressants, with an option of never (0), monthly (1), weekly (2) and daily (3). It appears that the scale does not evaluate noticeable problems (i.e., impairment) or distress that is an essential manifestation of substance use disorder; this assessment scale may show only recreational drinking or smoking. This makes it difficult to interpret the findings of this study whether it is referring recreational drinker or problematic alcohol users.

[Minor comments]

1) In Table 2, the prevalence of males having at least mild depressive symptoms is shown as 70.5% (n=235). According to my calculation it is 49.5% (n/N=235/475 = 0.4947), please check.

2) In Table 3, alcohol use in the last 3 months is shown as 173 (24.6%). The denominator should be all total substance users, 173/(28+25+173+33+24)=61.1%, please check.

3) English editing is needed.

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4 Sep 2020

Responses to reviewer comments

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Response: thank you. We have now uploaded the dataset as an additional file along with the revised manuscript.

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"This research was funded by Debre Markos University. But, the views in this study were fully

that of the authors and were not that of the funder.

TB is also financially supported by the Africa Mental Health Research Initiative (AMARI) within the

DELTAS Africa Initiative [DEL-15-01] as a post-doctoral fellow. The DELTAS Africa Initiative is an

independent funding scheme of the African Academy of Sciences (AAS)’s Alliance for Accelerating

Excellence in Science in Africa (AESA) and supported by the New Partnership for Africa’s Development

Planning and Coordinating Agency (NEPAD Agency) with funding from the Wellcome Trust [DEL-15-

01] and the UK government. TB was also supported financially by Debre Markos University."

We note that you have provided funding information that is not currently declared in your Funding Statement. However, funding information should not appear in the Acknowledgments section or other areas of your manuscript. We will only publish funding information present in the Funding Statement section of the online submission form.

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"The funders had no role in study design, data collection and analysis, decision to

publish, or preparation of the manuscript."

Response: thank you indeed. We have now noted that our funding section submitted during our online submission stated as "The funders had no role in study design, data collection and analysis, decision to

publish, or preparation of the manuscript." We will update the funding information during submission. The update of the funding section will be made as follows. "This research was funded by Debre Markos University. But, the views in this study were fully

that of the authors and were not that of the funder.

TB is also financially supported by the Africa Mental Health Research Initiative (AMARI) within the

DELTAS Africa Initiative [DEL-15-01] as a post-doctoral fellow. The DELTAS Africa Initiative is an

independent funding scheme of the African Academy of Sciences (AAS)’s Alliance for Accelerating

Excellence in Science in Africa (AESA) and supported by the New Partnership for Africa’s Development

Planning and Coordinating Agency (NEPAD Agency) with funding from the Wellcome Trust [DEL-15-

01] and the UK government."

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Response: thank you. We have no figure in this manuscript

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Response:

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

Response: we have now formatted the manuscript according the journal’s formatting guidelines.

________________________________________

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: No

Response: thanks for the comments of the reviewers on statistical aspects that guided as to revisit the statistical analysis again. In the current version of the manuscript, we have made modifications in Table 2, 3 and 4. We have checked the figures in the descriptive Table 2 and 3 using statistical package which was done using hand calculator. We have also added the descriptive for lifetime prevalence of substances in Table 2.

________________________________________

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: No

Response: we will be uploading the data accordingly. Thank you.

________________________________________

4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: No

Response: We have now carefully, edited the manuscript for language edits.

________________________________________

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The authors aimed to investigate the prevalence and risk factors of depressive symptoms and substance use among university students in North-Western Ethiopia. Focusing on depression and substance use is quite significant both from a clinical and public health perspective. However, several points should be critically considered.

[Major comments]

The authors assert the importance of clinical depression and substance abuse; however, this cross-sectional study assesses the level of depressive symptoms and substance use that compromise with a flaw, limiting the clinical relevance which needs to be considered.

Response: PHQ-9 is DSM based and very common tool in low income countries to assess depressive symptoms. It has been locally validated in Ethiopia with cut off of five and above indicating depressive symptoms. People with PHQ-9 score of five and above have functional impairment and above a cut off 10 or more is clinical level as suggested in validation studies. Indeed, we assume that the findings have clinical relevance taking the limitations into account. We have changed the substance use assessment scores in count data to reduce limitation of the substance use scale. Use of some of the substance like shisha and cannabis are very rare and illegal in Ethiopia. We also focused only on the last three month data than the lifetime to focus on severity though we inserted the lifetime prevalence for interested readers.

Moreover, We preferred the cross sectional survey as a first step just to know the prevalence of the problem. We plan to conduct clinical based research once we knew the extent of the problem. Hopefully, we will conduct clinical and intervention based design to help adolescent university students who are depressed due to substance use.

The authors report that the prevalence of mild levels of depressive symptoms to be about 30%, and that of major depressive symptoms to be about 40%. However, the mean (SD) PHQ-9 score of the sample is not given, which makes it ambiguous whether the sample has marked depression symptoms that may cause noticeable problems in relationships with others and day-to-day school activities (functional impairment). The mean (SD) PHQ-9 score of the sample should be provided. The authors also report “mild” and “major” depressive symptoms based on PHQ-9; however, the score range of mild and major depressive symptoms category is not given.

Response: thank you we have now provided the mean and standard deviation of the PHQ-9 score at the bottom row of in Table 1 while interpreting it in the text on page 11 of the manuscript. The cut off score was reported in the abstract section of the manuscript. in the current version, we have also included in the main body under “assessment” section (page 9).*-------

The authors also report that substance use was assessed by a composite scale the asking the lifetime and the three months experience of using five substances: khat, alcohol, tobacco, shisha, and depressants, with an option of never (0), monthly (1), weekly (2) and daily (3). It appears that the scale does not evaluate noticeable problems (i.e., impairment) or distress that is an essential manifestation of substance use disorder; this assessment scale may show only recreational drinking or smoking. This makes it difficult to interpret the findings of this study whether it is referring recreational drinker or problematic alcohol users.

Response: We have changed the substance use assessment scores into count data to reduce limitation of the substance use scale. Use of some of the substance like shisa and cannabis are very rare and almost deviant behavior in Ethiopia. We also focused only on the last three month data than the lifetime to focus on severity though we inserted the lifetime prevalence for interested readers.

We have tried to check whether the respondents showed depressive symptoms or not due to substance use. Though not to the level of impairment, students reported that they used substances to escape from worries related to academic pressure , stress which may ultimately lead them to be dependent on these substance and unable to function without them.

[Minor comments]

1) In Table 2, the prevalence of males having at least mild depressive symptoms is shown as 70.5% (n=235). According to my calculation it is 49.5% (n/N=235/475 = 0.4947), please check.

Response: Check. Yes, the last column was calculated by hand from the remaining cells obtained from SPSS cross tabulation. So, that was typo error. Thank you

2) In Table 3, alcohol use in the last 3 months is shown as 173 (24.6%). The denominator should be all total substance users, 173/(28+25+173+33+24)=61.1%, please check.

Response: the figure is referring to the prevalence and the denominator is the sample size. We have now made modifications and checked the figures for table 3.

3) English editing is needed.

Response: we have made careful language edits to the manuscript

________________________________________

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Reviewer #1: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

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________________________________________

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Submitted filename: Response to Reviewers.docx

Click here for additional data file.

6 Oct 2020

Perceived learning difficulty associates with depressive symptoms and substance use among students of higher educational institutions in North Western Ethiopia: A cross sectional study

PONE-D-20-08001R1

Dear Dr. Bitew,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Yutaka J. Matsuoka, MD, PhD

Academic Editor

PLOS ONE

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: RE: PONE-D-20-08001 R1

The authors aimed to investigate the prevalence and risk factors of depressive symptoms and substance use among university students in North-Western Ethiopia. Points raised in the peer review were adequately addressed.

[Major comments]

The authors assert the importance of clinical depression and substance abuse; however, this cross-sectional study assesses the level of depressive symptoms and substance use that compromise with a flaw, limiting the clinical relevance which needs to be considered.

>>Authors state that they preferred the cross sectional survey as a first step just to know the prevalence of the problem. And have changed the substance use assessment scores into a count data to reduce limitation of the substance use scale, and focused only on the last three month data than the lifetime to focus on severity.

The authors report that the prevalence of mild levels of depressive symptoms to be about 30%, and that of major depressive symptoms to be about 40%. However, the mean (SD) PHQ-9 score of the sample is not given, which makes it ambiguous whether the sample has marked depression symptoms that may cause noticeable problems in relationships with others and day-to-day school activities (functional impairment). The mean (SD) PHQ-9 score of the sample should be provided. The authors also report “mild” and “major” depressive symptoms based on PHQ-9; however, the score range of mild and major depressive symptoms category is not given.

>>Authors have provided the mean and standard deviation of the PHQ-9 score in Table 1.

The authors also report that substance use was assessed by a composite scale the asking the lifetime and the three months experience of using five substances: khat, alcohol, tobacco, shisha, and depressants, with an option of never (0), monthly (1), weekly (2) and daily (3). It appears that the scale does not evaluate noticeable problems (i.e., impairment) or distress that is an essential manifestation of substance use disorder; this assessment scale may show only recreational drinking or smoking. This makes it difficult to interpret the findings of this study whether it is referring recreational drinker or problematic alcohol users.

>>Authors have changed the substance use assessment scores into a count data to reduce limitation of the substance use scale.

[Minor comments]

1) In Table 2, the prevalence of males having at least mild depressive symptoms is shown as 70.5% (n=235). According to my calculation it is 49.5% (n/N=235/475 = 0.4947), please check.

>>Table 2 has been revised.

2) In Table 3, alcohol use in the last 3 months is shown as 173 (24.6%). The denominator should be all total substance users, 173/(28+25+173+33+24)=61.1%, please check.

>>Table 3 has been revised.

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

19 Oct 2020

PONE-D-20-08001R1

Perceived learning difficulty associates with depressive symptoms and substance use among students of higher educational institutions in North Western Ethiopia: A cross sectional study

Dear Dr. Bitew:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

If we can help with anything else, please email us at plosone@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

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on behalf of

Dr. Yutaka J. Matsuoka

Academic Editor

PLOS ONE