Lonely in Depression

Effects of Loneliness in the Treatment of Depression

The goal of this prospective study is to better understand the link between loneliness and depression in the inpatient psychiatric treatment of depression. It aims to answer:

Do lonely and not lonely persons benefit the same way from inpatient depression treatment? Is loneliness a clinical relevant factor in inpatient treatment of depression? What are the underlying biopsychosocial mechanisms?

Participants will be asked to do some

• self-report questionnaires
• clinical interview
• biosampling (blood, saliva, stool) at three main measurement timepoints (1. begin of inpatient treatment, 2. day of discharge, 3. three months after discharge).

Study Overview

• Status: Recruiting
• Conditions: Loneliness; Depression Disorder

Detailed Description

Loneliness and depression are widespread and severely debilitating health conditions. Notably, loneliness and depression are closely intertwined, with individuals suffering from depression being particularly vulnerable to loneliness. However, little is known regarding the clinical significance of loneliness in the treatment of depression and the biopsychosocial mechanisms underlying this association.

To examine the clinical relevance of the interplay between loneliness and depression, a prospective, noninterventional longitudinal design will be adopted. The study will be performed at the University Hospital and the community hospital in Erlangen, Germany. Every patient admitted to the hospital with depressive symptoms is eligible for screening according to the inclusion and exclusion criteria. Three main measurement points (T0, T1, and T2) and brief interim measurements conducted at two-week intervals (t0.1 to t0.X and t1.1-t1.6) will be utilized. After screening and clinical interviews, participants will complete the baseline measurements (T0). Thereafter, each participant will adhere to an individual period corresponding to the duration of that specific patient's inpatient stay at the clinic until the second measurement is obtained (T1). Follow-up will occur three months after T1.

Given that the effect sizes of the interaction between loneliness and depression in a clinical population are currently unknown, the sample size for this study was determined based on considerations of practicability and the population generalizability of the obtained results, as well as statistical plausibility.

To ensure the external validity of the results, it is important that both severely lonely depressive patients and less lonely depressive patients, as well as different disease trajectories and patient characteristics (e.g., age, sex, and number of comorbidities), can be identified. A sample size of approximately 200 participants is expected to ensure sufficient heterogeneity. This sample size is practically feasible due to the fact that, even when considering an inclusion rate of 50% and a dropout rate of 30% for the primary diagnosis of depression at the University Hospital and the community hospital in Erlangen, the recruitment potential clearly exceeds the target number of cases within an estimated period of two years.

Without the knowledge of which measured level of loneliness at baseline represents a strong level of loneliness and which measured level represents a weak level of loneliness in a depressed patient population, a median split of loneliness at baseline will be performed to calculate the statistical significance of the interaction between loneliness and depression in the inpatient and follow-up course (T0, T1, and T2). To detect a significant interaction effect of a mixed analysis of variance (ANOVA), when considering an α error of 0.05, a power of 0.9 (1-β error probability) and a correlation value among repeated measures of 0.5 for the groups defined as highly lonely and slightly lonely groups, the number of cases was calculated by using G*Power Version 3.1.9.7. Assuming a small effect size (f= 0.10), the desired sample size would be determined at n= 214 individuals; moreover, assuming a medium effect size (f= 0.25), the sample size would be n= 36 individuals. This indicates that there is statistical plausibility for detecting interaction effects between loneliness and depression with the target number of cases.

Eligibility screening and clinical diagnostic screening, along with interviews, are conducted by study physicians. Depression is assessed during a clinical interview (MADRS) by the patient's treatment team, which also determines when the patient will be discharged from the hospital. All of the self-report assessments are collected by the patients themselves by using the REDCap online survey application. Biosampling will be exclusively performed among participants recruited at the University Hospital to ensure methodologically consistent and rapid processing. Routine clinical data are primarily extracted from clinical documentation systems and consolidated prior to analysis (similar to other data sources).

Given that the study design does not permit definitive causal conclusions to be determined regarding the direction of effects, the findings are expected to provide valuable insights and relevant implications. In particular, the following insights can be obtained: (1) a report on whether more or less lonely patients receive equal benefits from inpatient multimodal depression treatment; (2) insights into changes in loneliness during and after depression treatment; (3) important findings regarding the shared and nonshared biopsychosocial mechanisms underlying loneliness and depression; and (4) the effects of loneliness and depression with respect to secondary outcomes, including quality of life and suicidality.

• Study Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

• Study Contact: Name: Franziska Sonnauer, Dr. med., M.Sc.; Phone Number: 00499131-8534597; Email: franziska.sonnauer@uk-erlangen.de
• Study Contact Backup: Name: Franca Fries, Dr. med.; Phone Number: 004991317530; Email: Franca.Fries@bezirkskliniken-mfr.de

Study Locations

• Germany
  • Bavaria
    • Erlangen, Bavaria, Germany, 91054
      • Recruiting
      • Friedrich-Alexander-Universität Erlangen-Nürnberg
      • Contact: Franziska Sonnauer, Dr. med.; Phone Number: 00499131-8534597; Email: einsamkeit-depression.ps@uk-erlangen.de
      • Principal Investigator: Franziska Sonnauer, Dr. med.
      • Sub-Investigator: Johannes Kornhuber, Prof. Dr. med.
      • Sub-Investigator: Daniel Blasko, Dr. med.
      • Sub-Investigator: Ilka Scheer
    • Erlangen, Bavaria, Germany, 91056
      • Not yet recruiting
      • Bezirkskliniken Mittelfranken, Clinic for Psychiatry, Addiction, Psychotherapie and Psychosomatic Medicine
      • Contact: Franca Laura Fries, Dr. med.; Phone Number: 004991317535353; Email: Franca.Fries@bezirkskliniken-mfr.de
      • Contact: Maksym Druzenko; Phone Number: 004991317535353; Email: Maksym.Druzenko@bezirkskliniken-mfr.de
      • Principal Investigator: Franca Laura Fries, Dr. med.
      • Sub-Investigator: Maksym Druzenko

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Individuals who are admitted for inpatient treatment at one of the two psychiatric clinics in Erlangen (university hospital, community hospital), Germany, either electively or as an emergency case, due to depressive symptoms.

Description

Inclusion Criteria:

• primary diagnosis of depression according to ICD-10 (F32 or F33), as diagnosed by a physician or clinical psychologist in conjunction with the M.I.N.I. Mini-International Neuropsychiatric Interview diagnostic tools
• inpatient elective or emergency admission to one of the two psychiatric clinics; - age over 18 years
• sufficient understanding of spoken and written German
• informed voluntary consent

Exclusion Criteria:

• a current lack of capacity to provide consent (e.g., pronounced psychotic symptoms, stuporous depressive syndrome, and thought constriction to suicidality)
• previous participation in the study
• pregnancy or breastfeeding
• inpatient stay of less than 7 days, even if the patients initially met the inclusion criteria.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Depression	Montgomery-Åsberg Depression Rating Scale (MADRS) (10 Items, each item rated 0-6 points, minimum 0 points, maximum 60 points, higher scores indicate greater severity of depressive symptoms)	Baseline/T0 (recruitment, normally day 1 of inpatient stay and maximum of day 4), T1 (end of inpatient stay, normally 7 days up to 50 weeks), Follow-Up/T2 (three months after clinical discharge); measured T0 to T1 and T0 to T2 and T1 to T2
Loneliness	3 Item UCLA Loneliness Scale (3-Item UCLA) (3 items, each item rated 1-3 points, minimum 3 points, maximum 9 points, higher scores indicate greater loneliness)	Baseline/T0 (recruitment, normally day 1 of inpatient stay and maximum of day 4), T1 (end of inpatient stay, normally 7 days up to 50 weeks), Follow-Up/T2 (three months after clinical discharge); measured T0 to T1 and T0 to T2 and T1 to T2
Depression	Patient Health Questionnaire, 9-Item Depression Scale (PHQ-9) (9 Items, each item rated 0-4 points, minimum 0 points, maximum 27 points, higher scores indicate greater severity of depression)	Baseline/T0 (recruitment, normally day 1 of inpatient stay and maximum of day 4), T1 (end of inpatient stay, normally 7 days up to 50 weeks), Follow-Up/T2 (three months after clinical discharge); measured T0 to T1 and T0 to T2 and T1 to T2
Loneliness	6-Item short scales for Loneliness, De Jong Gierveld Loneliness Scale (6-Item DJGLS) (6 Items, each item rated 1-3 points, before the total score is calculated, the items are dichotomized, thus resulting in a sum score ranging from 0 to 6, wherein scores of 0-1 indicate no loneliness, 2-4 indicate moderate loneliness, and 5-6 indicate severe loneliness)	Baseline/T0 (recruitment, normally day 1 of inpatient stay and maximum of day 4), T1 (end of inpatient stay, normally 7 days up to 50 weeks), Follow-Up/T2 (three months after clinical discharge); measured T0 to T1 and T0 to T2 and T1 to T2

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Social Support	Fragebogen zur Sozialen Unterstützung (F-SoZ-U 14) (14 Item shortend form, each item rated 0-4 points, minimum 0 points, maximum 56 points, higher total scores indicating higher levels of perceived social support)	Baseline/T0 (recruitment, normally day 1 of inpatient stay and maximum of day 4), T1 (end of inpatient stay, normally 7 up to 50 weeks), Follow-Up/T2 (three months after clinical discharge); measured T0 to T1 and T0 to T2 and T1 to T2
Inpatient treatment duration	in days	Baseline/T0 (recruitment, normally day 1 of inpatient stay and maximum of day 4) to T1 (end of inpatient stay, normally 7 up to 50 weeks).
Quality of life in self-report	World Health Organization-Five Well-Being Index (WHO-5) (5 Items, each item rated 0-5 points, minimum 0 points, maximum 25 points, the total score (0-25) is transformed to a scale ranging from 0 to 100, with scores ≤50 indicating diminished well-being and higher scores representing higher well-beeing)	Baseline/T0 (recruitment, normally day 1 of inpatient stay and maximum of day 4), T1 (end of inpatient stay, normally 7 days up to 50 weeks), Follow-Up/T2 (three months after clinical discharge); measured T0 to T1 and T0 to T2 and T1 to T2
Social Network measure (newly designed for this study)	As there is no culture and language adapted version of a social network indice available an adapted and German-translated version is used to capture participants' social interaction partners during the prior two weeks. The questionnaire was newly developed, with item content informed by existing validated scales (Cohen Social Network Index (SNI), Lubben Social Network Scale (LSNS), Berkman - Social Network/Integration). Via the use of a yes/no response format, participants indicated whether they had personal or telephone contact with each of the following: (1) spouse or partner, (2) own children, (3) parents or parent-like figures, (4) other relatives (e.g., siblings, uncles, or aunts), (5) friends, (6) neighbors, (7) colleagues, (8) people known through voluntary activities, (9) in-laws (parents, sons, or daughters-in-law), and (10) members of their social group (e.g., community, congregation, sports, or music clubs). Higher total scores indicate greater social connectedness.	Baseline/T0 (recruitment, normally day 1 of inpatient stay and maximum of day 4), T1 (end of inpatient stay, normally 7 days up to 50 weeks), Follow-Up/T2 (three months after clinical discharge); measured T0 to T1 and T0 to T2 and T1 to T2
General health status	Short Form 12 Health Survey (SF-12) (12 Items, Items rated 0-1, 1-3 and 1-5 and 1-6 scores represent eight dimensions of physical and mental well-beeing with two composite scores, items are recodet, z-transformed and normed, higher values indicate better health)	Baseline/T0 (recruitment, normally day 1 of inpatient stay and maximum of day 4), T1 (end of inpatient stay, normally 7 days up to 50 weeks), Follow-Up/T2 (three months after clinical discharge); measured T0 to T1 and T0 to T2 and T1 to T2
Social Anxiety	Social Phobia Inventory (SPIN) (17 Items, each item rated 0-4 points, minimum 0 points, maximum 68 points, higher scores indicate greater severity of social anxiety, three subscales are available (fear 6 items, avoidance 7 items, physiological distress 4 items))	Baseline/T0 (recruitment, normally day 1 of inpatient stay and maximum of day 4), T1 (end of inpatient stay, normally 7 days up to 50 weeks), Follow-Up/T2 (three months after clinical discharge); measured T0 to T1 and T0 to T2 and T1 to T2
Somatic Symptom Burden	13-Item Somatic Symptom Severity Scale of the Patient Health Questionnaire (PHQ-13) (13 Items, each item rated 0-2 points, minimum 0 points, maximum 34 points, higher values indicating more somatic symptoms)	Baseline/T0 (recruitment, normally day 1 of inpatient stay and maximum of day 4), T1 (end of inpatient stay, normally 7 days up to 50 weeks), Follow-Up/T2 (three months after clinical discharge); measured T0 to T1 and T0 to T2 and T1 to T2

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood markers (metabolic, LDL)	LDL cholesterin [mg/dl or mmol/l], higher values (> 100 mg/dl or > 2.6 mmol/l) represent unfavorable metabolic risk	Baseline/T0 (recruitment, normally day 1 of inpatient stay and maximum of day 4), T1 (end of inpatient stay, normally 7 days up to 50 weeks), Follow-Up/T2 (three months after clinical discharge); measured T0 to T1 and T0 to T2 and T1 to T2
Blood markers (metabolic, HDL)	HDL cholesterin [mg/dl or mmol/l), < 40 mg/dl men and < 50 mg/dl women represents unfavorable metabolic risk, ≥ 40 mg/dl men ≥ 50 mg/dl women acceptable, ≥ 60 mg/dl protective	Baseline/T0 (recruitment, normally day 1 of inpatient stay and maximum of day 4), T1 (end of inpatient stay, normally 7 days up to 50 weeks), Follow-Up/T2 (three months after clinical discharge); measured T0 to T1 and T0 to T2 and T1 to T2
Blood markers (metabolic, HbA1c)	HbA1c [%], higher values (> 5.7%) represent unfavorable metabolic risk	Baseline/T0 (recruitment, normally day 1 of inpatient stay and maximum of day 4), T1 (end of inpatient stay, normally 7 days up to 50 weeks), Follow-Up/T2 (three months after clinical discharge); measured T0 to T1 and T0 to T2 and T1 to T2
Blood markers (Sphingolipid metabolism)	Sphingolipid metabolism enzyme activity of secretory acid sphingomyelinase (S-ASM) [nmol/mL/h/µL], higher leveles represent more inflammation/apoptosis enzyme activity of neutral acid sphingomyelinase (N-ASM) [nmol/mL/h/µL], higher levels represent cellular stress/apotosis Ceramide [nmol/L], higher levels represent more inflammation/apoptosis	Baseline/T0 (recruitment, normally day 1 of inpatient stay and maximum of day 4), T1 (end of inpatient stay, normally 7 days up to 50 weeks), Follow-Up/T2 (three months after clinical discharge); measured T0 to T1 and T0 to T2 and T1 to T2
Blood markers (neutrotrophic factor, BDNF)	brain-derived neurotrophic factor [ng/mL], higher levels represent more neuroplasticity	Baseline/T0 (recruitment, normally day 1 of inpatient stay and maximum of day 4), T1 (end of inpatient stay, normally 7 days up to 50 weeks), Follow-Up/T2 (three months after clinical discharge); measured T0 to T1 and T0 to T2 and T1 to T2
Blood markers (hormonal)	Cortisol [µg/dL or nmol/L] and timepoint of blood test higher levels represent more stress response	Baseline/T0 (recruitment, normally day 1 of inpatient stay and maximum of day 4), T1 (end of inpatient stay, normally 7 days up to 50 weeks), Follow-Up/T2 (three months after clinical discharge); measured T0 to T1 and T0 to T2 and T1 to T2
Blood markers (immunological markers)	C-reactive protein (CRP) [mg/L], higher levels show systemic inflammation	Baseline/T0 (recruitment, normally day 1 of inpatient stay and maximum of day 4), T1 (end of inpatient stay, normally 7 days up to 50 weeks), Follow-Up/T2 (three months after clinical discharge); measured T0 to T1 and T0 to T2 and T1 to T2
Saliva marker (cortisol)	saliva cortisol (awakening and before bedtime), higher levels represent more stress response	Baseline/T0 (recruitment, normally day 1 of inpatient stay and maximum of day 4), T1 (end of inpatient stay, normally 7 days up to 50 weeks), Follow-Up/T2 (three months after clinical discharge); measured T0 to T1 and T0 to T2 and T1 to T2
Saliva marker (α-amylase)	saliva α-amylase activity [U/ml] (awakening and before bedtime), higher levels represent more stress response	Baseline/T0 (recruitment, normally day 1 of inpatient stay and maximum of day 4), T1 (end of inpatient stay, normally 7 days up to 50 weeks), Follow-Up/T2 (three months after clinical discharge); measured T0 to T1 and T0 to T2 and T1 to T2
Stool markers	alpha-diversity	Baseline/T0 (recruitment, normally day 1 of inpatient stay and maximum of day 4), T1 (end of inpatient stay, normally 7 days up to 50 weeks), Follow-Up/T2 (three months after clinical discharge); measured T0 to T1 and T0 to T2 and T1 to T2
Suicidality (clinician rated)	measures in clinical interview (Montgomery-Åsberg Depression Rating Scale (MADRS)) (Item No. 10 out of 10 items, rated 0-6, higher values represent more suicidality)	Baseline/T0 (recruitment, normally day 1 of inpatient stay and maximum of day 4), T1 (end of inpatient stay, normally 7 days up to 50 weeks), Follow-Up/T2 (three months after clinical discharge); measured T0 to T1 and T0 to T2 and T1 to T2
Suicidality (self-report)	9-Item Patient Health Questionnaire (PHQ-9) (Item No. 9 out of 9, rated 0-3 with higher scores indicating more suicidality)	Baseline/T0 (recruitment, normally day 1 of inpatient stay and maximum of day 4), T1 (end of inpatient stay, normally 7 days up to 50 weeks), Follow-Up/T2 (three months after clinical discharge); measured T0 to T1 and T0 to T2 and T1 to T2
Response (depression)	≥ 50% reduction in Montgomery-Åsberg Depression Rating Scale (MADRS) score from T0 to T1 (10 Items, each item rated 0-6 points, minimum 0 points, maximum 60 points, higher scores indicate greater severity of depressive symptoms)	Baseline/T0 (recruitment, normally day 1 of inpatient stay and maximum of day 4) to T1 (end of inpatient stay, normally 7 days up to 50 weeks).
Relapse (depression)	≥ 10 points more from T1 to T2 in Montgomery-Åsberg Depression Rating Scale (MADRS) score or ≥ 22 points at T2 (10 Items, each item rated 0-6 points, minimum 0 points, maximum 60 points, higher scores indicate greater severity of depressive symptoms)	T1 (end of inpatient stay/discharge from clinic) to Follow-Up/T2 (three months after clinical discharge).
Antidepressant medication	consideration of these classes of antidepressant drugs if these are given in a dosage that is effective as an antidepressant (e.g. for Mirtazapin not 7.5 mg, starting from 15 mg): SSRI/SNRI/NaSSA(Mirtazapin)/NDRI (Buproprion)/TZA/MAO-I/SARI (Trazodon)Agomelatin/other with classes of augmentation strategy: Lithium/antipsychotics/second antidepressant/other augmentation strategy sorted as: antidepressant monotherapy/antidepressant augmented therapy/other and change in therapy stategy (1. no; 2. yes drug substance (2.1) added/ (2.2) changed/ (2.3) removed; 3. yes dosage of antidepressant changed (3.1) increased/(3.2) decreased; 4. augmentation strategy changed)	Baseline/T0 (recruitment, normally day 1 of inpatient stay and maximum of day 4), T1 (end of inpatient stay, normally 7 days up to 50 weeks), Follow-Up/T2 (three months after clinical discharge); measured T0 to T1 and T0 to T2 and T1 to T2
trait vs. state loneliness	Given the absence of an established measure capable of differentiating between enduring (trait) and situational (state) loneliness, this aspect is captured by using a newly developed single item: 'In looking back upon my life, I would say that I have felt …'. Participants respond to this item on a four-point scale (1= mostly lonely throughout my life, 2= lonely from time to time, 3= only lonely at present, and 4= never lonely). Responses of 1 are intended to represent trait loneliness; options 2 and 3 represent state loneliness; and option 4 indicates no loneliness.	Baseline/T0 (recruitment, normally day 1 of inpatient stay and maximum of day 4), T1 (end of inpatient stay, normally 7 days up to 50 weeks), Follow-Up/T2 (three months after clinical discharge); measured T0 to T1 and T0 to T2 and T1 to T2
number of therapies participated	frequency per week of psychotherapy, group interventions and other	Baseline/T0 (recruitment, normally day 1 of inpatient stay and maximum of day 4) to T1 (end of inpatient stay, normally 7 days up to 50 weeks).

Collaborators and Investigators

• Sponsor: Friedrich-Alexander-Universität Erlangen-Nürnberg
• Collaborators: Bezirkskliniken Mittelfranken, Clinic for Psychiatry, Addiction, Psychotherapie and Psychosomatic Medicine, Am Europakanal, Germany
• Investigators: Principal Investigator: Franziska Sonnauer, Dr. med., M.Sc., Department of Psychiatry and Psychotherapy, Friedrich-Alexander Universität Erlangen-Nürnberg

Study record dates

Study Major Dates

• Study Start (Actual): February 5, 2026
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: December 2, 2025
• First Submitted That Met QC Criteria: December 31, 2025
• First Posted (Actual): January 12, 2026

Study Record Updates

• Last Update Posted (Actual): February 24, 2026
• Last Update Submitted That Met QC Criteria: February 23, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: depression; prospective; clinical; loneliness; biosampling
• Additional Relevant MeSH Terms: Behavioral Symptoms; Behavior; Depression
• Other Study ID Numbers: 25-435-B

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: IPD used in the results publication No final desicion has been made as several partners are involved and feasibility and regulatory requirements are still under review.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No