Converging Evidence Points to BDNF as Biomarker of Depressive Symptoms in Schizophrenia-Spectrum Disorders
Abstract
:1. Introduction
2. Materials and Methods
2.1. Design and Settings
2.2. Clinical Assessments
2.2.1. Psychopathological Measures
2.2.2. Social Functioning and Quality of Life Measures
2.2.3. Cognitive Assessment
2.3. Assessment of BDNF Serum Levels and Genotyping
2.4. Statistical Analysis
3. Results
3.1. Sample Characteristics
3.2. Associations of Clinical Variables with BDNF Levels
3.3. Multiple Linear Regression Analysis
3.4. Analysis of BDNF Genetic Variants
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Variable (Continuous) | N | Mean | SD |
BDNF serum levels, ng/mL | 105 | 25.45 | 13.67 |
Age, years | 105 | 48.85 | 10.45 |
Education, years | 105 | 9.26 | 3.23 |
Offspring, N | 105 | 0.34 | 0.95 |
Age of onset, years | 105 | 21.77 | 9.30 |
Duration of illness, months | 105 | 308.51 | 134.33 |
Age at first treatment, years | 105 | 24.23 | 8.95 |
Duration of untreated illness, months | 105 | 29.07 | 54.60 |
Cigarettes smoked per day, N | 46 | 19.83 | 9.80 |
Weight, Kg | 74 | 77.32 | 18.76 |
Height, cm | 74 | 167.84 | 8.83 |
BMI | 73 | 27.30 | 6.80 |
Waist circumference, cm | 45 | 90.47 | 18.37 |
Antipsychotics, chlorpromazine equivalents, mg/die | 103 | 378.92 | 272.03 |
Variable (categorical) | N | % | |
Sex (male) | 74 | 70.5 | |
Marital status | |||
Single | 8 | 7.6 | |
Married/Cohabiting | 10 | 9.5 | |
Divorced | 2 | 1.9 | |
Widowed | 83 | 79.0 | |
NA | 2 | 1.9 | |
Presence of offspring | 19 | 18.1 | |
Employment | |||
Employed | 7 | 6.7 | |
Student | 1 | 1.0 | |
Registered disabled civilian | 95 | 90.5 | |
Unemployed | 2 | 1.9 | |
Presence of smoking | 52 | 49.5 | |
History of substance abuse | 28 | 30.8 | |
Current use of substances | 5 | 5.5 | |
Presence of family history of mental disorders | 64 | 61.0 | |
Presence of family history of schizophrenia | 31 | 29.5 | |
Presence of family history of bipolar disorder | 8 | 7.6 | |
Presence of family history of major depressive disorder | 19 | 18.1 | |
Presence of family history of anxiety disorders | 10 | 9.5 | |
Clinical course | |||
Episodic with full remission | 2 | 1.9 | |
Episodic with residual symptoms | 37 | 35.2 | |
Chronic with or without periodical relapses | 65 | 61.9 | |
NA | 1 | 1.0 | |
Presence of hospital admissions | 93 | 88.6 | |
Diagnosis of schizophrenia (SCID-I) | 64 | 61.0 | |
Diagnosis of schizoaffective disorder (SCID-I) | 41 | 39.0 | |
Diagnosis of obsessive-compulsive disorder (SCID-I) | 5 | 4.8 | |
Diagnosis of cluster A personality disorders (SCID-II) | 2 | 1.9 | |
Diagnosis of cluster B personality disorders (SCID-II) | 2 | 1.9 | |
Diagnosis of cluster C personality disorders (SCID-II) | 2 | 1.9 | |
Diagnosis of personality disorder NOS (SCID-II) | 1 | 1.0 | |
Long-acting antipsychotic therapy | 24 | 22.9 |
Psychometric Measure | N | Mean | SD |
---|---|---|---|
PAS childhood | 98 | 1.38 | 1.22 |
PAS early adolescence | 98 | 2.05 | 1.30 |
PAS late adolescence | 92 | 2.96 | 1.44 |
PAS adulthood | 80 | 3.13 | 1.70 |
PAS general | 97 | 3.43 | 1.24 |
PANSS, positive symptoms | 105 | 14.84 | 4.76 |
PANSS, negative symptoms | 105 | 19.38 | 6.56 |
PANSS, general psychopathology | 105 | 40.70 | 10.41 |
PANSS, total score | 105 | 74.92 | 17.93 |
CGI-SCH, severity positive symptoms | 105 | 3.30 | 1.37 |
CGI-SCH, severity negative symptoms | 105 | 3.25 | 0.94 |
CGI-SCH, severity depressive symptoms | 105 | 2.36 | 1.05 |
CGI-SCH, severity cognitive symptoms | 105 | 3.29 | 1.12 |
CGI-SCH, global severity | 105 | 3.60 | 0.96 |
PSP, total score | 105 | 50.60 | 14.18 |
WHOQOL, physical health | 101 | 12.91 | 2.71 |
WHOQOL, psychological | 101 | 12.08 | 1.78 |
WHOQOL, social relationship | 101 | 11.68 | 3.74 |
WHOQOL, environment | 101 | 12.11 | 2.35 |
BACS, verbal memory | 102 | 5.26 | 2.34 |
BACS, digit sequencing task (number of correct response) | 102 | 12.71 | 6.23 |
BACS, digit sequencing task (longest sequence recalled correctly) | 102 | 5.08 | 2.09 |
BACS, verbal fluency (category instances) | 102 | 9.14 | 5.05 |
BACS, verbal fluency (controlled oral word association test) | 102 | 16.25 | 7.93 |
BACS, attention, and speed of information processing (symbol coding) | 101 | 24.16 | 15.03 |
BACS, executive functions, Tower of London | 101 | 8.71 | 6.40 |
SWN, mental functioning | 100 | 15.97 | 4.23 |
SWN, self-control | 100 | 15.94 | 3.24 |
SWN, physical functioning | 100 | 16.29 | 4.33 |
SWN, emotional regulation | 100 | 16.22 | 3.67 |
SWN, social integration | 100 | 15.95 | 3.53 |
SWN, total score | 100 | 80.37 | 13.96 |
Demographic and Clinical Variable (Continuous) | BDNF Serum Levels (ng/mL) (rho) | p | N |
---|---|---|---|
Age, years | −0.1 | 0.33 | 105 |
Education, years | −0.09 | 0.36 | 105 |
Offspring, N | −0.01 | 0.88 | 105 |
Age of onset, years | −0.07 | 0.48 | 105 |
Length of current episode, months | −0.01 | 0.9 | 105 |
Age at first treatment, years | −0.18 | 0.06 | 105 |
Duration of illness, months | −0.12 | 0.90 | 105 |
Duration of untreated illness, months | −0.07 | 0.49 | 105 |
Cigarettes smoked per day, N | −0.02 | 0.91 | 46 |
Weight, Kg | 0.18 | 0.12 | 74 |
Height, cm | 0.11 | 0.35 | 74 |
BMI | 0.26 | 0.30 | 18 |
Waist circumference, cm | 0.08 | 0.6 | 45 |
PAS childhood | −0.28 | 0.01 | 98 |
PAS early adolescence | −0.2 | 0.07 | 98 |
PAS late adolescence | −0.12 | 0.3 | 92 |
PAS adulthood | −0.12 | 0.4 | 80 |
PAS general | −0.07 | 0.53 | 97 |
PANSS, positive symptoms | 0.03 | 0.75 | 105 |
PANSS, negative symptoms | −0.01 | 0.39 | 105 |
PANSS, general psychopathology | −0.004 | 0.97 | 105 |
PANSS, total score | −0.04 | 0.73 | 105 |
CGI-SCH, severity positive symptoms | 0.08 | 0.43 | 105 |
CGI-SCH, severity negative symptoms | −0.19 | 0.06 | 105 |
CGI-SCH, severity depressive symptoms | −0.32 | 0.001 | 105 |
CGI-SCH, severity cognitive symptoms | −0.12 | 0.21 | 105 |
CGI-SCH, global severity | −0.16 | 0.09 | 105 |
PSP, total score | 0.02 | 0.8 | 105 |
WHOQOL, physical health | −0.01 | 0.91 | 101 |
WHOQOL, psychological | 0.1 | 0.31 | 101 |
WHOQOL, social relationship | 0.07 | 0.47 | 101 |
WHOQOL, environment | 0.13 | 0.2 | 101 |
BACS, verbal memory | −0.03 | 0.79 | 102 |
BACS, digit sequencing task (number of correct response) | 0.06 | 0.54 | 102 |
BACS, digit sequencing task (longest sequence recalled correctly) | 0.04 | 0.69 | 102 |
BACS, verbal fluency (category instances) | 0.02 | 0.83 | 102 |
BACS, verbal fluency (controlled oral word association test) | 0.23 | 0.02 | 102 |
BACS, attention, and speed of information processing (symbol coding) | 0.005 | 0.96 | 101 |
BACS, executive functions, Tower of London | 0.04 | 0.72 | 101 |
SWN, mental functioning | 0.16 | 0.11 | 100 |
SWN, self-control | 0.07 | 0.49 | 100 |
SWN, physical functioning | 0.11 | 0.3 | 100 |
SWN, emotional regulation | 0.10 | 0.34 | 100 |
SWN, social integration | 0.11 | 0.29 | 100 |
SWN, total score | 0.16 | 0.10 | 100 |
Antipsychotics, chlorpromazine equivalents, mg/die | 0.08 | 0.38 | 103 |
Clinical Variable (Categorical) | BDNF Serum Levels (ng/mL), Mean (SD) | t or F | p | |
---|---|---|---|---|
Sex | Female | 24.5 (13.3) | 0.47 | 0.63 |
Male | 25.9 (13.9) | |||
Age class | 18–20 | 32.0 (8.8) | 1.6 | 0.5 |
21–25 | 24.9 (12.3) | |||
26–44 | 26.1 (14.7) | |||
45–65 | 21.0 (14.0) | |||
Marital status | Single | 29.5 (14.7) | 0.9 | 0.6 |
Married/Cohabiting | 18.6 (11.4) | |||
Divorced | 30.5 (26.7) | |||
Widowed | 25.5 (13.6) | |||
Presence of offspring | Yes | 25.2 (14.9) | 0.73 | 0.9 |
No | 25.5 (13.5) | |||
Employment | Employed | 28.5 (17.8) | 0.25 | 0.9 |
Student | 25.8 (NA) | |||
Registered disabled civilian | 25.1 (13.6) | |||
Unemployed | 32.5 (4.6) | |||
Presence of family history of mental disorders | Yes | 26.5 (14.1) | 0.4 | 0.9 |
No | 24.1 (13.1) | |||
Presence of family history of schizophrenia | Yes | 26.5 (14.8) | −0.5 | 0.6 |
No | 25.0 (13.3) | |||
Presence of family history of bipolar disorder | Yes | 27.1 (9.5) | −0.5 | 0.6 |
No | 25.3 (14.0) | |||
Presence of family history of major depressive disorder | Yes | 24.1 (14.2) | 0.4 | 0.6 |
No | 25.7 (13.6) | |||
Presence of family history of anxiety disorders | Yes | 26.0 (12.1) | −0.1 | 0.9 |
No | 25.4 (13.9) | |||
Clinical course | Episodic with full remission | 32.6 (5.8) | 0.1 | 0.9 |
Episodic with residual symptoms | 28.7 (14.7) | |||
Chronic with or without periodical relapses | 23.6 (12.9) | |||
Presence of hospital admissions | Yes | 25.6 (13.9) | −0.3 | 0.8 |
No | 24.4 (11.9) | |||
Presence of smoking | Yes | 27.1 (14.6) | −1.6 | 0.1 |
No | 22.4 (12.1) | |||
History of substance abuse | Yes | 23.8 (13.1) | 0.6 | 0.5 |
No | 25.7 (14.1 | |||
Current use of substances | Yes | 19.7 (10.9) | 0.9 | 0.4 |
No | 25.5 (13.9) | |||
Diagnosis | Schizophrenia | 24.9 (13.5) | 0.5 | 0.6 |
Schizoaffective disorder | 26.3 (14.0) | |||
Diagnosis of cluster A personality disorders (SCID-II) | Yes | 21.5 (14.2) | 0.4 | 0.7 |
No | 25.6 (13.7) | |||
Diagnosis of cluster B personality disorders (SCID-II) | Yes | 24.1 (15.4) | 0.2 | 0.9 |
No | 25.6 (13.7) | |||
Diagnosis of cluster C personality disorders (SCID-II) | Yes | 32.6 (23.6) | −0.43 | 0.5 |
No | 25.4 (13.6) | |||
Class of antipsychotics | First-generation | 25.7 (13.01) | −0.15 | 0.88 |
Second-generation | 25.3 (13.9) |
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Manchia, M.; Isayeva, U.; Collu, R.; Primavera, D.; Deriu, L.; Caboni, E.; Iaselli, M.N.; Sundas, D.; Tusconi, M.; Pinna, F.; Paribello, P.; Scherma, M.; Pisanu, C.; Meloni, A.; Zai, C.C.; Congiu, D.; Squassina, A.; Fratta, W.; Fadda, P.; Carpiniello, B. Converging Evidence Points to BDNF as Biomarker of Depressive Symptoms in Schizophrenia-Spectrum Disorders. Brain Sci. 2022, 12, 1666. https://doi.org/10.3390/brainsci12121666
Manchia M, Isayeva U, Collu R, Primavera D, Deriu L, Caboni E, Iaselli MN, Sundas D, Tusconi M, Pinna F, Paribello P, Scherma M, Pisanu C, Meloni A, Zai CC, Congiu D, Squassina A, Fratta W, Fadda P, Carpiniello B. Converging Evidence Points to BDNF as Biomarker of Depressive Symptoms in Schizophrenia-Spectrum Disorders. Brain Sciences. 2022; 12(12):1666. https://doi.org/10.3390/brainsci12121666
Chicago/Turabian StyleManchia, Mirko, Ulker Isayeva, Roberto Collu, Diego Primavera, Luca Deriu, Edoardo Caboni, Maria Novella Iaselli, Davide Sundas, Massimo Tusconi, Federica Pinna, Pasquale Paribello, Maria Scherma, Claudia Pisanu, Anna Meloni, Clement C. Zai, Donatella Congiu, Alessio Squassina, Walter Fratta, Paola Fadda, and Bernardo Carpiniello. 2022. "Converging Evidence Points to BDNF as Biomarker of Depressive Symptoms in Schizophrenia-Spectrum Disorders" Brain Sciences 12, no. 12: 1666. https://doi.org/10.3390/brainsci12121666