SYSTEMATIC REVIEW

published: 19 May 2020

doi: 10.3389/fpsyt.2020.00445

The Effects of Individual

Psychotherapy in BDNF Levels of
Patients With Mental Disorders: A
Systematic Review
Felipe Cesar de Almeida Claudino 1*, Leonardo Gonçalves 1, Felipe Barreto Schuch 2,
Hugo Roberto Sampaio Martins 3 and Neusa Sica da Rocha 1
1 Center of Clinical Research and Center of Experiamental Research, Hospital de Clı´nicas de Porto Alegre (HCPA), Post-
Graduation Program in Psychiatry and Behavioral Sciences, Federal University of Rio Grande do SUl (UFRGS), Porto Alegre,
Brazil, 2 Department of Sports Methods and Techniques, Federal University of Santa Maria (UFSM), Santa Maria, Brazil,
3 Department of Internal Medicine, Federal University of Health Sciences of Porto Alegre (UFCSPA), Porto Alegre, Brazil

Edited by:
Background: Brain-derived Neurotrophic Factor (BDNF) is considered the main cerebral
Takeshi Terao, neurotrophin and is produced in the central neural system and peripherals. Its levels are
Oita University, Japan
reduced in patients with several psychiatric disorders, but it is unclear if the response to
Reviewed by:
psychotherapy can alter its concentration.
Kenji Hashimoto,
Chiba University, Japan Objective: To carry out a systematic review evaluating the effects of individual
Reiji Yoshimura,
University of Occupational and
psychotherapy in BDNF levels in patients with mental disorders.
Environmental Health Japan, Japan Methods: The databases PubMed, EMBASE, PsycArticles, SciELO, Web of Science,
*Correspondence: and CENTRAL; the last search was performed on October 2019 for trials evaluating the
Felipe Cesar de Almeida Claudino
[email protected] effects of individual psychotherapy in BDNF levels in adults with mental disorders.
PROSPERO registration: CRD42018108144.
Specialty section:
This article was submitted to
Results: Eight of 293 studies were included. A rise in BDNF levels was observed in
Psychological Therapies, depressive patients when psychotherapy was combined with medication. Patients with
a section of the journal
post-traumatic stress disorder (PTSD) who responded to therapy presented a raise in
Frontiers in Psychiatry
BDNF levels mostly when combined with physical activity. There was a rise in BDNF levels
Received: 29 March 2020
Accepted: 01 May 2020 in those who responded to psychotherapy in patients with bulimia, in borderline patients,
Published: 19 May 2020 and in insomniacs.
Citation:
Claudino FCA, Gonçalves L,
Conclusions: The BDNF seems to present variations after psychotherapy especially in
Schuch FB, Martins HRS and patients with bulimia, PTSD, insomnia, and borderline. These subjects also have symptom
Rocha NS (2020) The Effects of reduction. Thereby, BDNF could be a supplemental tool to analyze the success to
Individual Psychotherapy in BDNF
Levels of Patients With Mental psychotherapy. BDNF levels in patients with major depression after therapy are still
Disorders: A Systematic Review. controversial and the short follow-up of most studies is a limiting factor.
Front. Psychiatry 11:445.
doi: 10.3389/fpsyt.2020.00445 Keywords: psychotherapy, brain derived neurotrophic factor, BDNF, mental disorders, systematic review

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Claudino et al. Effects of Psychotherapy in BDNF

INTRODUCTION mental disorders by qualified professionals and with its

pathology described in the Diagnostic and Statistical Manual of
Psychotherapy is a well-grounded treatment for mental disorders Mental Disorders (DSM V).
with outcomes similar to pharmacotherapy (1). Psychotherapeutic The interventions of interest for the study: in-person
interventions consist of exposure to stimuli, content resignification, individual psychotherapy: cognitive behavioral therapy,
and behavioral changes via interpersonal interaction (2). It acts on psychoanalysis, eye movement desensitization and reprocessing
cognition and leads to symptoms remission, the formation of new (EMDR), dialectical behavior therapy, interpersonal
neural networks, and can consequently lead to changes in demeanor psychotherapy, analytically-oriented psychotherapy, and
(3). The neurotrophins are peptides in the central nervous system, acceptance/commitment therapy, without limit of sessions or
and the most abundant is brain-derived neurotrophic factor (BDNF) length of treatment.
(4), which stands out among the responsible factors in the formation Control groups defined: patients with no mental disorders or
of new neural networks that result in improved symptomatology. patients with psychiatric disorders submitted to other
BDNF is a neurotrophin that is more concentrated in certain comparative treatments that are not psychotherapy, such as
regions of the brain such as the pre-frontal cortex and the physical activity, meditation, and electroconvulsotherapy.
hippocampus (5)—regions where complex cognitive processes For the outcome, BDNF levels and disorder symptoms
occur including memory, personality, and emotional control. (according to symptom scales) were measured at two different
Therefore, psychotherapy stimulates these areas (6) reflecting on times before and after psychotherapy exposure. Only serum or
psychological symptom remission and resulting in a rise in plasma BDNF levels were considered.
BDNF levels. We included longitudinal randomized or non-randomized
Peripheral BDNF concentrations are lower in people with clinical trials as well as prospective and retrospective cohort
neuropsychiatric and neurodegenerative diseases (7, 8) versus studies; there was no language restriction, and any year of
matched controls. There is also signaling interference of this publication was considered including studies in progress.
peptide in limbic areas related to emotion such as the
hippocampus (9) that may contribute to the maintenance of Exclusion Criteria
the diseases. Patients undergoing only group therapy, online therapy, those
BDNF levels also rise after antidepressant treatment, and without pre and post intervention BDNF serum or plasma levels,
increase in BDNF are associated with symptom improvements and patients who did not have their symptoms evaluated pre and
(10, 11); thus, it might be a potential mediator of the post intervention were not included. Cross-sectional or case
antidepressant treatment (12). Beyond pharmacological reports were not considered.
treatment, it is possible to observe increases in this
neurotrophin's levels via electroconvulsive therapy (13) and Search Strategy and Study Selection
physical activity (14) concurrent to the remission of The titles and/or abstracts were obtained by two independent
psychological symptoms. Previous reviews of psychotherapies evaluators (FC and HM) by searching the following databases in
showed few potential response biomarkers for this treatment in October 2019: PubMed, EMBASE, PsycArticles, Scielo, CENTRAL,
patients diagnosed with PTSD such as the 5-alfa-reductase, heart and Web of Science. The following terms were used for the research
rate changes (15), glucocorticoid metabolism, gene methylation, in PubMed: (“cognitive behavioral therapy” OR CBT OR “cognitive
(16) and structural brain changes (17). behavior therapy” OR “cognitive behavior treatment” OR
Despite the promising effects of psychotherapy response “cognitive-behavioral treatment” OR “cognitive behavior therapy”
biomarkers, there is no systematic review evaluating the effects OR “cognitive behaviour treatment” OR “cognitive behavioral
of individual psychotherapy in BDNF levels. Therefore, the therapy” OR “cognitive behavioural treatment”) OR
objectives of this study are to: 1) evaluate if there are any [(psychotherapy OR “psychotherapeutic processes”) OR
changes in BDNF levels in people with mental disorders “Cognitive Therapy” OR (“psychotherapy, brief” OR “short-
following individual psychotherapy and 2) evaluate if these duration psychotherapy”) OR “interpersonal therapy” OR
changes are associated with symptom improvement. “analytical psychotherapy” OR “eye movement desensitization
and reprocessing” OR EMDR] AND (“brain derived neurotrophic
factor” OR BDNF OR neurotrophin OR neurogenesis OR “nerve
METHODS cell plasticity” OR “brain plasticity” OR “nerve plasticity” OR
“neural plasticity” OR neuroplasticity). The terms were adjusted
Study Eligibility according to the protocols in each database.The searches in each
This review adhered to the Preferred Reporting Items for database were realized twice by two independent evaluators,
Systematic Reviews and Meta-Analyses (PRISMA) (18). The adapting pre-defined terms following the protocol for each base
protocol was registered on PROSPERO: CRD42018108144. (such as Mesh terms for PUBMED and thesaurus for Embase, for
example). In any divergence regarding the abstracts of each
Inclusion Criteria database, an independent third party realized a new search.
The study population defined: patients over 18 years old, both Independent search results were confronted and divergences were
genders, previously diagnosed with psychiatric disorders and/or resolved by a third independent party. Abstracts from “grey

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Claudino et al. Effects of Psychotherapy in BDNF

literature” were only considered if available in the randomized studies (Table 2) (28). This allows evaluation as
evaluated databases. “high”, “low”, or “unclear” risk of bias for each domain: selection,
The study selection was conducted in two steps. First, the title attrition, detection, performance, reporting, and others. The
and abstract of the articles obtained in the search were analyzed intra-study risk of bias was also included (Table 3). There was
by two independent authors (FC and HM) and selected no exclusion of articles, regardless of the score, due to the small
according to the inclusion and exclusion criteria. Next, the number of studies obtained, but the restrictions were considered
remaining articles were read in full. A third reviewer was when analyzing the individual results.
recruited in case of any disagreement on the inclusion or
exclusion of studies at any stage. Searches Results
A total of 4,895 references were found. Of these, 1,808 were
Data Extraction and Analysis duplicates and excluded. Thus, 3,087 abstracts were evaluated in
Two authors, independently, extracted data on the following terms of title and abstract followed by exclusion of 2,995 by
metrics, previously defined in pilot forms: year of publication, criteria shown in the figure below. At the full-text stage, 92
country, study design, patient precedence, sex, number of articles were read in full, and 8 articles were added to the review
participants, disorder type, therapy type, therapy length, total of and inspected followed by two proofreaders (Figure 1).
sessions, BDNF (plasma or serum), mean and standard deviation of
BDNF levels (pre and post intervention), symptom measures, and Main Mental Disorders Studied
complementary therapies (pharmacotherapy or else). The main features of the studies are detailed in Table 4. We
found studies evaluating BDNF levels in people with major
Assessment of Risk of Bias depressive disorder (k=3), PTSD (k=2), bulimia (k=1),
Two instruments were used to evaluate the “Assessment of risk borderline disorder (k=1), and sleep disorder (K=1) with a
of bias”: The New Castle-Ottawa (19) was indicated for predominance in women in five studies (55, 5–100%); three
longitudinal non-randomized studies. It evaluates aspects such studies have a predominance of male patients. The number of
as selection, comparability, and outcome (Table 1). Its scores patients varied between n=7 and n=115. Most patients came
vary between 0 (highest bias) to 9 points (lowest bias). The from outpatient clinics (k=4), and the treatment extent was 4
Cochrane Collaboration's tool assessed risk of bias for weeks to 12 months.

TABLE 1 | Evaluation of the methodological quality of longitudinal studies using the Newcastle-Ottawa scale.

Study Selection Comparability Outcome Total

Representativeness Selection of Ascertainment Outcome of interest was Comparability Assessment Follow-up Adequacy
the non not present at start of of outcome long of follow
exposed study enough up

Koch et * * ** * * 6
al. (20)
Yamada * * ** * * 6
et al. (21)
Park et * * ** * * 6
al. (22)
Perroud * * * ** * * 7
et al. (23)
Rusch et * * ** * * * 7
al. (24)

*Correspond to criteria (1 point).

**Correspond to criteria (2 points).

TABLE 2 | Evaluation of the methodological quality of randomized studies using Cochrane Collaboration's tool for assessing risk of bias for studies.

Silva et al. (25) Powers et al. (26) Yan et al. (27)

Domain
Random sequence generation Low risk Low risk Low risk
Allocation concealment Low risk Low risk Low risk
Blinding of participants and personnel Low risk Low risk Low risk
Blinding of outcome assessment Low risk Low risk Low risk
Incomplete outcome data Low risk Low risk Low risk
Selective reporting Low risk Low risk Low risk
Other sources of bias Low risk Low risk Low risk

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Claudino et al. Effects of Psychotherapy in BDNF

TABLE 3 | Evaluation of Intra-study bias risk of studies included.

Study Clear definition of the Clear definition of Independent results evaluation? (by Sufficient Selective loss Identified and
study population? results and evaluation? a third party, for example) follow-up during follow up? clear limitations?
time?

Koch YES YES NO NO NO YES

et al. (20)
Silva et al. YES YES NO YES NO YES
(25)
Powers YES YES NO YES NO NO
et al. (26)
Yamada YES YES NO NO NO YES
et al. (21)
Park et al. YES YES NO NO NO YES
(22)
Perroud YES YES NO NO NO YES
et al. (23)
Yan et al. YES YES NO YES NO YES
(27)
Rusch YES YES NO YES NO YES
et al. (24)

Main Clinical Measures Evaluated therapy: [baseline responders (mean ±SD): 3.3±.3.7 x non-
and Diagnosis Criteria responders 2.8±1.3 p=0.68; Day 21-responders: 3.4 ±3.6 x non-
The diagnostic criteria of the Diagnostic and Statistical Manual responders 3.1±2.3 p=0.97] (17) or Cognitive-Behavioral
of Mental Disorders IV (29, 30) (k=3), SIDES (Structured Therapy [pre-treatment (mean ±SD) 1.387±0.26; post-
Interviews for Disorders of Extreme Stress) (31) (k=1), Mini treatment 1.328±0.3, p= 0.294] (18). However, the responders
International Neuropsychiatric Interview (MINI-PLUS) (32) initially had a higher level of neurotrophin and a higher increase
(k=1), Classification and Diagnostic Criteria for Mental versus non-responders (17). In a study of medication associated
Disorder in China 3 (CCMD-3) (33), and Epworth Sleepiness with therapy, the group using only vortioxetine had a significant
Scale (ESS) (34) were used. Different scales were used for the difference in BDNF levels between intervention and control
symptom evaluation: Hamilton Depression Rating Scale (35), groups in baseline and after. The group who underwent CBT
(BDI) Beck Depression Inventory (36, 37), PTSD Symptom associated with medication had a significant increase versus the
Scale-Interview Version (38), State–Trait Anxiety Scale (39), control group (p<0.001) (27).
Clinical Global Impression Change Scale (CGI-CS) (40), (BIS- Two studies (19, 28) in PTSD patients have shown increased
10): Barrat Impulsiveness Scale (41), (CTQ): Childhood Trauma levels of BDNF after intervention in different modalities:
Questionnaire (42), (SCID-II): Screening Interview for Axis II exposure therapy (19) and eye movement desensitization and
Disorder (43), (PSIQI): Pittsburgh Sleep Quality Index (44), reprocessing (28). The first study related elevation of
(QIDS-SR): Quick Inventory of Depressive Symptomatology neurotrophin when psychotherapy was associated with
(45), (PCL-M): PTSD Checklist-Military Version (46), and physical activity (mean ±SD) (pre: 1.38 x post: 3.73). Their
(SF-36): Short From Health Survey-36 (47). values were not expressive in isolation (pre: 1.77 x post: 1.75)
All studies presented symptom reduction on these scales. and PSSI: PE (prolonged exposure therapy): (mean ±SD) 37.00
Three articles branched the patients into responders depending (8.25); PE+ Exercise: 42.00 (5.2) (19). However, the second study
on the reduction of 50% of the HAMD (20) or BDI (23). baseline indicated that patients who presented a clinical response or
and CGI-C scores above the “much improved” level after symptom remission symptoms had higher increases in BDNF
therapy (22) than those who did not respond to treatment [responders: (mean
±SD 4435.6±1273.4; non-responders 2789±643.2; p 0.025)].
Complementary Psychopharmacotherapy There was an association between the increase of BDNF levels
Three of the articles included psychopharmacotherapy as a and symptoms reduction such as anxiety, phobia, and
complementary therapy. Those diagnosed with insomnia could dissociation after EMDR in patients with PTSD (19).
use automatic positive airway pressure (APAP). Only one study At baseline, patients with bulimia nervosa undergoing eye
included physical activity versus complementary therapy (19). movement desensitization and reprocessing had reduced BDNF
Six of the eight studies analyzed plasma levels of BDNF, and two values versus controls (p = 0.02)—this has been established in
opted for serum levels. previous studies. This sample presented elevation of BDNF levels
which were more expressive among responders than non-
Psychotherapy, Scales, and BNDF Levels responders. The pre and post therapy scale scores of
The main results of individual studies are described in Table 5. responders are listed here: BDI pre (mean ±SD) 22±11.9, post:
No significant changes in BDNF levels were observed in 17.4±15.2, p=0.22, STAI-state pre: 56±12.9, post 50±17.7,
depressive patients and those who submitted to interpersonal p=0.07, STAI-trait pre: 65.8±10.1, post: 55.2±18.5, p 0.08 (13).

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Claudino et al. Effects of Psychotherapy in BDNF

FIGURE 1 | PRISMA flowchart of article selection (18).

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Claudino et al. Effects of Psychotherapy in BDNF

TABLE 4 | Characteristics of included studies.

Study N Design Complementary Setting patient Time BDNF Clinical Measure

(M/F) Therapy extraction

Koch et al. (20) 27 Not randomized Without medication Inpatient and 12-16 Plasma HAMD
(12/ outpatient sessions
15) (6 weeks)
Silva et al. (25) 42 Randomized clinical Without medication Outpatient 16 sessions Serum BDI-II
(7/35) trial (12 weeks)
Powers et al. (26) 9 Randomized clinical ET + Exercise No information 12 sessions Plasma PSSI
(1/8) trial psychopharmacological (12 weeks)
Yamada et al. 8 Not randomized Without medication Outpatient 4 weeks Plasma EDI, BDI and STAI
(21) (8/0)
Park et al. (22) 7 Not randomized Without medication (*) No information 8 sessions Plasma CGI
(0/7)
Perroud et al. 115 Not randomized psychopharmacological Outpatient 4 weeks Plasma BDI, BIS-10, CTQ, SCID-II
(23) (7/
108)
Yan et al. (27) 41 Randomized clinical psychopharmacological No information 12 months Serum HAMD
(22/ trial
19)
Rusch et al. (24) 44 Not randomized APAP Outpatient 4-8 biweekly Plasma PSQI, QIDS-SR, PCL-M, SF-
psychopharmacological 36

APAP, automatic positive airway pressure; BDI II, Beck Depression Inventory II; BDI, Beck Depression Inventory; BIS-10, Barrat Impulsiveness Scale; CGI-CS, Clinical Global Impression
Change Scale; CTQ, Childhood Trauma Questionnaire; EDI, Eating Disorder Inventory; ET, Exposure therapy ; HAMD, Hamilton Depression Rating Scale; PCL-M, PTSD Checklist-Military
Version; PSIQI, Pittsburgh Sleep Quality Index; PSSI, PTSD Symptom Scale-Interview; QIDS-SR, Quick Inventory of Depressive Symptomatology; SCID-II, Screening Interview for Axis II
Disorder; SF-36, Short Form Health Survey-36; STAI, State–Trait Anxiety Scale. (*) 2 mg lorazepam or 10 mg diazepam was allowed for sleep management.

TABLE 5 | Main results.

Study Diagnosis Therapy MAIN RESULTS

(20) Major (IPT) • 17 patients had a reduction of the least 50% on the baseline Hamilton scale score and were defined as “responders” after
Depressive psychotherapy.
Disorder • BDNF had no meaningful difference between the responders and non-responders groups.
• Age, sex, HAMD, subject as inpatient or outpatient, number of previous depressive events, or pharmacological treatment
before the therapy had no meaningful correlation with BDNF levels.
• There were no association between BDNF levels and depression severity
(25) Major (CBT) • There was a significantly depression symptoms reduction after psychotherapy.
Depressive • There were no significant differences between pre and post psychotherapy intervention BDNF levels.
Disorder
(26) Post-traumatic (ET) • Psychotherapy, as only treatment, in patients with PTSD did not change BDNF levels in 12 weeks.
stress disorder • Exposure therapy associated with physical activity increased the BDNF levels in patients.
(22) Post-traumatic (EMDR) • There were no meaningful changes on BDNF plasma levels after psychotherapy, but responders presented higher BNDF
stress disorder plasma levels than non-responders.
• Anxiety, phobia, and dissociation levels were significantly reduced after EMDR.
• BDNF basal levels presented correlation with the depression and anxiety estimated response
(21) Bulimia (CBT) • BDNF levels in patients with bulimia increased after treatment.
Nervosa • There were no differences between BDNF levels in inpatients and outpatients
• There was a reduction in the frequency of self-induced vomiting, laxatives using, and compulsive eating episodes after
therapy.
• There were no significant changes on the Beck Depression Inventory and Eating Disorder Inventory scores, except for “Drive
for Thinness”.
(23) Borderline (I-DBT) • Plasma BDNF levels in subjects with BPD were higher than in the control group
Disorder • There was an inversely proportional decrease of BDNF levels in response to psychotherapy
• Non-responders had a reduction of BDNF levels after psychotherapy and, responders, had an increase, both, not significant.
(27) Major (CBT) • After the treatment, the group that underwent pharmacotherapy combined with psychotherapy presented a most expressive
Depressive depressive symptom reduction in comparison to the submitted only to the pharmacological treatment.
Disorder • Before the treatment, both control and intervention group had BDNF levels with no significant differences. After intervention,
the group with psychotherapy associated presented a significantly higher increase of BDNF
(24) Sleep Disorder (CBT) • The group that had an improvement on sleep patterns had a not significant BDNF increase, while in the group that its sleep
patterns got worse, BDNF levels did not change.

CBT, Cognitive-Behavioral Therapy; EMDR, Eye Movement Desensitization and Reprocessing; ET, Exposure Therapy; I-DBT, Intensive dialectical behavior therapy; IPT, Interpersonal
therapy.

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Claudino et al. Effects of Psychotherapy in BDNF

Borderline personality diagnosed patients had a higher BDI patients using medication associated with psychotherapy had an
mean than the healthy control group (mean ± SD 34.10±11.8) increased BDNF.
similar to other symptom scales. Responders had an insignificant Although there is initial evidence for the role of BDNF as an
increase in plasma BDNF levels (p=0.062), as non-responders individual psychotherapy response biomarker, the heterogeneity
had insignificant reduction (p=0.78) (23). across the studies limit the conclusions of this meta-analysis—
Finally, patients with sleep disorders were divided between the groups had different disorders, types of therapies, therapy
those who presented an improved sleep pattern and those who exposure times, and others boundary conditions that may affect
got worse. The first group presented an insignificant BDNF increase the results. The literature is restricted to depression, PTSD,
(pre: 80.2± 28.6; post 89.1±36.3; p =0.089). BDNF levels were bulimia, insomnia, and borderline disorders. Thus, the
stable in the group with no improvement (pre: 91.7±38.1; post conclusions cannot be extended to other disorders like bipolar
100.2±44.4; p=0.155) (27). disorder and anxiety disorders.
We also cannot disregard the relevance of polymorphism
knowledge in response to psychotherapies. A biological response
marker could also be expanded to other biomarkers.
DISCUSSION Longitudinal studies evaluating BDNF levels in response to
To the best of our knowledge, this is the first systematic review to psychotherapy could facilitate the performance of a meta-
evaluate the relation between BDNF levels in response to analysis of such candidate biomarkers.
psychotherapies. The results showed that, in general, there was
a reduction of clinical symptoms in patients with mental Limitations
disorders that went through different kinds of psychotherapies. The conclusions of this review must be cautious because the
In most cases, there was also a concurrent rise in BDNF levels. studies included in this review are small, most of which with a
In central nervous system, the levels of BDNF are higher in short follow up period. As to BDNF values, the included studies
structures of the limbic system, such as the hippocampus (48) quantified serum and plasma BDNF levels and there is evidence
and, in patients with mental disorders, the neurotrophin that the levels of these molecules change according to analyzed
concentration in this region is reduced (49). Meanwhile, the tissue and organs (59, 60) Also, it isn't possible to quantify the
psychotherapy has the potential for stimulation of the limbic proBDNF precursor and its derivatives values: mature BDNF
system and (50), although the physiology is not clear until this and pro-peptide BDNF. It is relevant to know this data, for there
moment, we can assume que psychotherapies act in this system, is evidence that they have different effects in the physiopathology
stimulating a higher BDNF production, reducing of psychiatric disorder (61). As well, age (62) and ethnicity (63)
psychiatric symptoms. may interfere in BDNF levels and also were not considered while
While this present review showed that there is no absolute quantifying the neurotrophin.
consensus regarding BDNF levels rise after psychotherapy, there
is meta-analysis that shows evidence of the increase of BDNF
after pharmacological treatment (51, 52). Although both
treatments are recognized as effective, this difference can be CONCLUSION
explained by the short follow-up time of the patients. The
In conclusion, there is a nascent body of evidence evaluating the
response to pharmacological therapy tends to occur faster (53),
effects of individual psychotherapies on BDNF. These
while the response to psychotherapy may take months (54),
neurotrophins seem to present variations after psychotherapy
depending on factors such as therapeutic relation, for
especially in patients with bulimia, PTSD, insomnia, and
example (55).
borderline personality, and that show reductions in symptoms.
These findings showed initial evidence that BDNF could be a
In patients with depression, those who submitted only to
potential tool to evaluate the effect of psychotherapies on patients
psychotherapy had no increase in BDNF levels while patients
with mental disorders. The BDNF levels could be used with
with associated medicine usage showed an obviously higher
symptom evaluation and other tools such as clinical symptom
increase versus those who submitted solely to pharmacological
scales to confirm that there is a satisfactory response to therapy.
treatment. There is only one study with a higher than 12-week
Furthermore, BDNF levels tend to be stable over time (56), and
follow-up period, which suggests that a longer follow-up time is
psychotherapy can be a variable course. Thus, such levels might
needed for BDNF levels. BDNF could supplement symptom
change at a different rate versus those observed here. Only one of
scales to analyze the effects of psychotherapy.
our manuscripts had a follow-up longer than 12 weeks. Prior
reviews and meta-analyses have shown that there is an increase in
BDNF levels in depressive patients treated with pharmacologically
(57) or with physical activity (58). Healthy patients have stable DATA AVAILABILITY STATEMENT
BDNF levels over time, which favors the theory that patients with
mental disorders submitted to therapies have an increase in The data set obtained for this study are available from
neurotrophins as an outcome. However, in this review, only corresponding author on request.

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Claudino et al. Effects of Psychotherapy in BDNF

AUTHOR CONTRIBUTIONS FUNDING

FC: preparation and registration of the review protocol, This study was financed in part by the Coordenação de
extraction of articles in the databases, selection of articles, Aperfeiçoamento de Pessoal de Nível Superior–Brasil
analysis of results, and article production. LG: protocol (CAPES)—Finance Code 001 and by Hospital de Clínicas de
production, results analysis, and article production. FS: Porto Alegre Research Incentive Fund (FIPE).
protocol production, results analysis, and article production.
HM: preparation of the review protocol, extraction of articles
in the databases, selection of articles, analysis of results, and ACKNOWLEDGMENTS
article production. NR: main orientation, protocol production,
review of articles in case of divergence, analysis of results, and FC is supported by a doctoral scholarship from Coordenacão de
article production. Aperfeiçoamento de Pessoal de Nı́vel Superior (CAPES), Brazil.

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