Refeeding syndrome and psychopharmacological interventions in children and adolescents with Anorexia Nervosa: a focus on olanzapine-related modifications of electrolyte balance.

This study aims to investigate the potential correlation between the use of olanzapine, a psychopharmacological intervention commonly prescribed in Anorexia Nervosa treatment, and the occurrence of Refeeding Syndrome. Despite the acknowledged nutritional and biochemical impacts of olanzapine, the literature lacks information regarding its specific association with Refeeding Syndrome onset in individuals with Anorexia Nervosa. This is a naturalistic, retrospective, observational study, reporting the occurrence of Refeeding Syndrome in children and adolescents with Anorexia Nervosa, treated or untreated with olanzapine. Dosages and serum levels of olanzapine were assessed for potential associations with the occurrence of Refeeding Syndrome and specific variations in Refeeding Syndrome-related electrolytes. Overall, 113 patients were enrolled, including 46 (41%) who developed a Refeeding Syndrome. Mild (87%), moderate (6.5%), and severe (6.5%) Refeeding Syndrome was described, at a current average intake of 1378 ± 289 kcal/day (39 ± 7.7 kcal/kg/die), frequently associated with nasogastric tube (39%) or parenteral (2.2%) nutrition. Individuals receiving olanzapine experienced a more positive phosphorus balance than those who did not (F(1,110) = 4.835, p = 0.030), but no difference in the occurrence of Refeeding Syndrome was documented. The mean prescribed doses and serum concentrations of olanzapine were comparable between Refeeding Syndrome and no-Refeeding Syndrome patients.    Conclusion: The present paper describes the occurrence of Refeeding Syndrome and its association with olanzapine prescriptions in children and adolescents with Anorexia Nervosa. Olanzapine was associated with a more positive phosphorus balance, but not with a different occurrence of Refeeding Syndrome. Further, longitudinal studies are required. What is Known: • Refeeding Syndrome (RS) is a critical complication during refeeding in malnourished patients, marked by electrolyte (phosphorus, magnesium, potassium) imbalances. • Olanzapine, an atypical antipsychotic with nutritional and biochemical impacts, is used in Anorexia Nervosa (AN) treatment, however data concerning its association with RS are lacking. What is New: • The study observed RS in 46/113 (41%) young patients with AN. • Olanzapine-treated individuals showed a higher improvement in serum phosphate levels than untreated ones, although no impact on the occurrence of Refeeding Syndrome was observed.

Olanzapine for young PEople with aNorexia nervosa (OPEN): A protocol for an open-label feasibility study.

INTRODUCTION: Antipsychotics are routinely prescribed off-label for anorexia nervosa (AN) despite limited evidence. This article presents a protocol of a study aiming to assess the feasibility of a future definitive trial on olanzapine in young people with AN. METHODS AND ANALYSIS: In an open-label, one-armed feasibility study, 55 patients with AN or atypical AN, aged 12-24, receiving outpatient, inpatient or day-care treatment who are considered for olanzapine treatment will be recruited from NHS sites based in England. Assessments will be conducted at screening, baseline and at 8-, 16 weeks, 6- and 12 months. Primary feasibility parameters will be proportions of patients who agree to take olanzapine and who adhere to treatment and complete study assessments. Qualitative methods will be used to explore acceptability of the intervention and study design. Secondary feasibility parameters will be changes in body mass index, psychopathology, side effects, health-related quality of life, carer burden and proportion of participants who would enrol in a future randomised controlled trial. The study is funded by the National Institute for Health Research via Health Technology Assessment programme. DISCUSSION: Olanzapine for young PEople with aNorexia nervosa will inform a future randomised controlled trial on the efficacy and safety of prescribing olanzapine in young people with AN.

Psilocybin for anorexia nervosa: If it helps, let's learn how.

Existing treatments for adults with anorexia nervosa (AN) have limited effectiveness. AN is a brain-based disorder with behavioral and cognitive features leading to severe undernourishment. Peck et al. conducted a small open trial suggesting safety and tolerability of psilocybin for AN,1 opening an avenue for further investigation into the neural mechanisms involved.

Psilocybin therapy for females with anorexia nervosa: a phase 1, open-label feasibility study.

Anorexia nervosa (AN) is a deadly illness with no proven treatments to reverse core symptoms and no medications approved by the US Food and Drug Administration. Novel treatments are urgently needed to improve clinical outcomes. In this open-label feasibility study, 10 adult female participants (mean body mass index 19.7 kg m-2; s.d. 3.7) who met Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for AN or pAN (partial remission) were recruited to a study conducted at an academic clinical research institute. Participants received a single 25-mg dose of synthetic psilocybin in conjunction with psychological support. The primary aim was to assess safety, tolerability and feasibility at post-treatment by incidences and occurrences of adverse events (AEs) and clinically significant changes in electrocardiogram (ECG), laboratory tests, vital signs and suicidality. No clinically significant changes were observed in ECG, vital signs or suicidality. Two participants developed asymptomatic hypoglycemia at post-treatment, which resolved within 24 h. No other clinically significant changes were observed in laboratory values. All AEs were mild and transient in nature. Participants' qualitative perceptions suggest that the treatment was acceptable for most participants. Results suggest that psilocybin therapy is safe, tolerable and acceptable for female AN, which is a promising finding given physiological dangers and problems with treatment engagement. ClinicalTrials.gov identifier NCT04661514 .

The role of risperidone in the treatment of children and adolescents with anorexia nervosa.

BACKGROUND: Current Diagnostic and Statistical Manual of Mental Disorders (DSM)-5-based research provides limited data on the use of risperidone on children and adolescents with anorexia nervosa (AN) mainly in small-sample/case report studies. AIM: To report the use of risperidone in a group of children and adolescents with feeding and eating disorders, specifically with AN. METHODS: Observational, naturalistic study. Psychopathology was assessed with Eating Disorders Inventory-3, Beck's Depression Inventory-II, and Symptom Checklist-90-R. Data were reported for the whole sample, for patients treated with risperidone, and finally compared between patients with AN treated with risperidone and those receiving no atypical antipsychotics. Potential differences in admission-discharge changes in body mass index (BMI) and psychopathology were assessed with analyses of covariance corrected for baseline measures. Kaplan-Meier analyses were conducted to assess retention rates of risperidone (at 3 months and 1 year) and rates of rehospitalization on 1-year follow-up. RESULTS: The study enrolled 120 patients with AN (42 treated with risperidone). Risperidone was used for 116.7 (±122.8) days (total exposure = 3979 days) and well-tolerated (nausea, asthenia in one case). No significantly different admission-discharge improvements for BMI or psychopathology were documented for patients treated with risperidone. Risperidone showed a 3-month retention rate of 50.0% (1 year: 9.5%) and was discontinued mainly for the resolution of target symptoms. Cumulative freedom from rehospitalization at 12 months was comparable for treated and untreated patients (hazard ratio = 1.088; Log-rank p = 0.908). CONCLUSIONS: This study reports real-life evidence of the use of risperidone in AN children and adolescents in the widest described sample so far. Longitudinal research should assess long-term prognostic factors and tolerability.

Omega-3 as an adjuvant in the treatment eating and psychological symptoms in patients with anorexia nervosa: a systematic review and meta-analyses.

BACKGROUND: This study was carried out to assess the effects of omega-3 supplementation as an adjunct treatment for eating and psychological symptoms in patients with anorexia nervosa. METHODS: We conducted a systematic review of the literature using the terms 'anorexia nervosa' AND 'Fatty Acids, Omega-3'. Five randomised controlled trials with a total of 144 participants, published between 2003 and 2022, were included. RESULTS: The effects of supplementation of omega-3 on anxiety were standardised mean difference (SMD) 0.79, 95% confidence interval (CI) -0.08 to 1.66; p = 0.08; I² = 3%; two studies, 33 participants; moderate quality of evidence. For depression, the supplementation of omega-3 was SMD: 0.22, 95% CI: -0.50 to 0.93; p = 0.18; I² = 45%; two studies, 33 participants; moderate quality of evidence. For obsessive-compulsive disorder, the supplementation of omega-3 was SMD: -0.22, 95% CI: -0.70 to 2.25; p = 0.36; I² = 0%; three studies, 32 participants; low quality of evidence. CONCLUSION: This research showed that regardless of dose, time or, if associated with other components, the use of omega-3 supplementations as an adjuvant treatment showed no evidence of effect in eating and psychological symptoms in patients with anorexia nervosa.

The Role of Mood Stabilizers in Children and Adolescents with Anorexia Nervosa: A 1-year Follow-Up, Propensity Score-Matched Study.

BACKGROUND: The existing literature on the use of mood stabilizers (MS) in children and adolescents with anorexia nervosa (AN) is limited, for the most part, to small case studies. METHODS: This was an observational, naturalistic, propensity score-matched study. Subjects treated and not-treated with MS were compared by being matched via propensity score on age, sex, concurrent atypical antipsychotics, and concurrent antidepressants. General and AN-specific psychopathology was assessed with Symptom Check List-90-R, Beck Depression Inventory-II, Eating Disorders Inventory-3, and Body Uneasiness Test-A. Potential differences in admission-discharge modifications (body mass index (BMI), psychopathology) among the two groups were assessed. Finally, re-hospitalizations after 1-year follow-up were assessed with Kaplan-Meier analyses. RESULTS: The study enrolled 234 hospitalized patients (15.9+/-3.3 years; 26, 11.1% receiving MS). After propensity-score matching, 26 MS patients matched with 26 MS-not-treated subjects were included. MS were used for a mean of 126.1 (+/-87.3) days, and two cases of side effects were documented (alopecia and somnolence with valproate). No significant difference between MS-treated and not-treated patients emerged concerning admission-discharge improvements in BMI and AN-specific or general psychopathology. The cumulative survival from re-hospitalization at 12 months was 64,4% (95%-CI, 31.3-97.5) for MS and 58.7% (95%-CI, 22.2-95.2) for MS-not-treated subjects. No significant difference in survival rate emerged (hazard ratio, 0.04; Log-rank test: p=0.846). CONCLUSIONS: This propensity score-matched study expands on the scant existing evidence of the use and side effects of MS in children and adolescents with AN. These results should be assessed in wider longitudinal samples.

A small-molecule degrader of TET3 as treatment for anorexia nervosa in an animal model.

Anorexia nervosa (AN) is a psychiatric illness with the highest mortality. Current treatment options have been limited to psychotherapy and nutritional support, with low efficacy and high relapse rates. Hypothalamic AgRP (agouti-related peptide) neurons that coexpress AGRP and neuropeptide Y (NPY) play a critical role in driving feeding while also modulating other complex behaviors. We have previously reported that genetic ablation of Tet3, which encodes a member of the TET family dioxygenases, specifically in AgRP neurons in mice, activates these neurons and increases the expression of AGRP, NPY, and the vesicular GABA transporter (VGAT), leading to hyperphagia and anxiolytic effects. Bobcat339 is a synthetic small molecule predicted to bind to the catalytic pockets of TET proteins. Here, we report that Bobcat339 is effective in mitigating AN and anxiety/depressive-like behaviors using a well-established mouse model of activity-based anorexia (ABA). We show that treating mice with Bobcat339 decreases TET3 expression in AgRP neurons and activates these neurons leading to increased feeding, decreased compulsive running, and diminished lethality in the ABA model. Mechanistically, Bobcat339 induces TET3 protein degradation while simultaneously stimulating the expression of AGRP, NPY, and VGAT in a TET3-dependent manner both in mouse and human neuronal cells, demonstrating a conserved, previously unsuspected mode of action of Bobcat339. Our findings suggest that Bobcat339 may potentially be a therapeutic for anorexia nervosa and stress-related disorders.

Intranasal administration of olanzapine has beneficial outcome in a rat activity-based anorexia model.

The atypical antipsychotic drug olanzapine is prescribed despite clinical studies on olanzapine treatment showing mixed results on treatment efficacy in anorexia nervosa. We investigated the effect of systemic and intranasal administration of olanzapine in the activity-based anorexia (ABA) model. Rats were habituated to a running wheel and exposed to the ABA model while treated with olanzapine. During ABA rats had 1.5 h of daily access to food and ad libitum access to a running wheel for seven consecutive days. Olanzapine was administered via an osmotic minipump (1, 2.75, and 7.5 mg/kg) or intranasally 2 h before dark onset (1 and 2.75 mg/kg). We monitored body weight, food intake, wheel revolutions, body temperature, and adipose tissue. We found 2.75 and 7.5 mg/kg systemic olanzapine decreased wheel revolutions during ABA. Relative adipose tissue mass was increased in the 7.5 mg/kg olanzapine-treated group while body weight, food intake, and body temperature were unaltered by the systemic olanzapine. 1 and 2.75 mg/kg intranasal olanzapine diminished wheel revolutions and body temperature during the first 2 h after administration. The intranasal olanzapine-treated rats had a higher body weight at the end of ABA. We find that olanzapine has beneficial outcomes in the ABA via two administration routes by acting mainly on running wheel activity. Intranasal olanzapine showed a rapid effect in the first hours after administration in reducing locomotor activity. We recommend further exploring intranasal administration of olanzapine in anorectic patients to assist them in coping with restlessness.

Premenarchal anorexia nervosa: clinical features, psychopharmacological interventions, and rehospitalization analysis in a 1-year follow-up, controlled study.

Premenarchal anorexia nervosa (AN) represents a specific subtype of AN, defined by an onset before the menarche in females, involving unique endocrine and prognostic features. The scarce data on this condition lack case-control and follow-up studies. This is a case-control, observational, naturalistic study, involving participants with premenarchal AN (premenarchal girls presenting to the study center newly diagnosed with AN) treated with a multidisciplinary hospital intervention, compared to postmenarchal AN individuals on clinical, endocrine, psychopathological, and treatment variables. The rate of rehospitalizations on a 1-year follow-up after discharge and respective prognostic factors were assessed with a Kaplan-Meier analysis and Cox regression model. The sample included 234 AN participants (43, 18.4% with premenarchal and 191, 81.6% with postmenarchal AN). When compared to postmenarchal, premenarchal AN individuals presented with lower depressive scores (Self-Administered Psychiatric Scales for Children and Adolescents (SAFA)) (U = 1387.0, p = 0.010) and lower luteinizing hormone (LH) levels (U = 3056.0, p = 0.009) and were less frequently treated with antidepressants (X2 = 5.927, p = 0.015). A significant predictive model of the risk of rehospitalization (X2 = 19.192, p = 0.004) identified a higher age at admission (B = 0.522, p = 0.020) and a day-hospital (vs inpatient) treatment (B = 3957, p = 0.007) as predictive factors for rehospitalization at 1-year, independent from the menarchal status.   Conclusion: This study reports the clinical and treatment characteristics of premenarchal AN in one of the largest samples available in the current literature. Specific clinical features and prognostic factors for rehospitalization at 1-year follow-up were identified. Future studies should longitudinally investigate treatment-dependent modifications in endocrine and psychopathological measures in this population. What is Known: • Premenarchal Anorexia Nervosa (AN) is a subtype of AN characterized by its onset before menarche in females and is associated with unique endocrine and prognostic features. What is New: • Individuals with premenarchal AN may display specific clinical profiles, with lower depressive symptoms and luteinizing hormone levels than postmenarchal controls.

Efficacy and tolerance of second-generation antipsychotics in anorexia nervosa: A systematic scoping review.

INTRODUCTION: Second-generation antipsychotics (SGAs) are frequently prescribed for the treatment of resistant anorexia nervosa. However, few clinical trials have been conducted so far and no pharmacological treatment has yet been approved by the Food and Drug Administration. The aim of this paper is to conduct a systematic scoping review exploring the effectiveness and safety of atypical antipsychotics in anorexia nervosa (AN). METHOD: We conducted a systematic scoping review of the effectiveness and tolerability of SGAs in the management of AN. We included articles published from January 1, 2000, through September 12, 2022 from the PubMed and PsycInfo databases and a complementary manual search. We selected articles about adolescents and adults treated for AN by four SGAs (risperidone, quetiapine, aripiprazole or olanzapine). This work complies with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for scoping reviews (PRIMA-ScR) and was registered in the Open Science Framework (OSF) repository. RESULTS: This review included 55 articles: 48 assessing the effectiveness of SGAs in AN and 7 focusing only on their tolerability and safety. Olanzapine is the treatment most frequently prescribed and studied with 7 randomized double-blind controlled trials. Other atypical antipsychotics have been evaluated much less often, such as aripiprazole (no randomized trials), quetiapine (two randomized controlled trials), and risperidone (one randomized controlled trial). These treatments are well tolerated with mild and transient adverse effects in this population at particular somatic risk. DISCUSSION: Limitations prevent the studies both from reaching conclusive, reliable, robust, and reproducible results and from concluding whether or not SGAs are effective in anorexia nervosa. Nonetheless, they continue to be regularly prescribed in clinical practice. International guidelines suggest that olanzapine and aripiprazole can be interesting in severe or first-line resistant clinical situations.

Novel ketamine and zinc treatment for anorexia nervosa and the potential beneficial interactions with the gut microbiome.

Anorexia nervosa (AN) is a severe illness with diverse aetiological and maintaining contributors including neurobiological, metabolic, psychological, and social determining factors. In addition to nutritional recovery, multiple psychological and pharmacological therapies and brain-based stimulations have been explored; however, existing treatments have limited efficacy. This paper outlines a neurobiological model of glutamatergic and γ-aminobutyric acid (GABA)-ergic dysfunction, exacerbated by chronic gut microbiome dysbiosis and zinc depletion at a brain and gut level. The gut microbiome is established early in development, and early exposure to stress and adversity contribute to gut microbial disturbance in AN, early dysregulation to glutamatergic and GABAergic networks, interoceptive impairment, and inhibited caloric harvest from food (e.g., zinc malabsorption, competition for zinc ions between gut bacteria and host). Zinc is a key part of glutamatergic and GABAergic networks, and also affects leptin and gut microbial function; systems dysregulated in AN. Low doses of ketamine in conjunction with zinc, could provide an efficacious combination to act on NMDA receptors and normalise glutamatergic, GABAergic and gut function in AN.

Through the looking glass: Skin signs that help diagnose eating disorders.

Eating disorders (EDs) such as anorexia nervosa and bulimia nervosa have a plethora of skin manifestations. They can be categorized into skin signs of self-purging, skin signs of starvation, skin signs related to drug abuse, skin signs of psychiatric comorbidity, and miscellaneous signs. "Guiding signs" are valuable because they are pointers to the diagnosis of an ED. They include hypertrichosis (lanugo-like hair), Russell's sign (knuckle calluses), self-induced dermatitis, and perimylolysis (tooth enamel erosion). Practitioners should recognize such skin signs promptly, as this helps to diagnose early, which may improve the prognosis of ED. Management requires a multidisciplinary approach that focuses on psychotherapy combined with attention to medical complications, nutritional needs, and nonpsychiatric findings such as cutaneous manifestations. Psychotropic medications that are currently used in EDs include pimozide and atypical antipsychotic agents, such as aripiprazole and olanzapine, fluoxetine, and lisdexamfetamine.

A retrospective study of pharmacological treatment in anorexia nervosa: 6-month and 12-month follow-up.

BACKGROUND: Anorexia nervosa (AN) is a serious and potentially life-threatening eating disorder characterized by starvation and malnutrition, a high prevalence of coexisting psychiatric conditions, marked treatment resistance, frequent medical complications, and a substantial risk of death. Body mass index (BMI) is a key measure of treatment outcome of AN and it is necessary to evaluate the long-term prognosis of AN. This study aimed to better assess the BMI course trend between different medications and timepoints in order to improve AN treatment in clinical practice. METHODS: During the period 2010-2021, we retrospectively reviewed historical data of all patients diagnosed with AN. There were two groups in this study, which were based on the duration of follow-up. Group A was a 6-month follow-up group, comprising 93 patients (mean age 19.6 ± 6.8 years), with BMI assessed at three consecutive time points: first outpatient visit (T0), three months follow-up (T3), and six months follow-up (T6). Group B was a 12-month follow-up group comprising 36 patients (mean age 17.0 ± 5.2 years) with BMI assessed at five consecutive time points: first outpatient visit (T0), three months follow-up (T3), six months follow-up (T6), nine months follow-up (T9), and twelve months follow-up (T12). In our study, we retrospectively compared BMI courses based on patients' usage of medication using the following variables: single medication, switching medications, combined medications, and without medications. The primary outcome measurement was BMI recorded at the 6-month follow-up and the 12-month follow-up respectively. In our study, which was conducted at Taichung Veterans General Hospital, we reviewed outpatient medical records of all patients with AN who were seen at the hospital during the period 2010-2021. RESULTS: In Group A (6-month follow-up), patients treated with antidepressants showed a mean BMI increase of 1.3 (p < 0.001); patients treated with antipsychotics showed a mean BMI increase of 1.1 (p = 0.01); patients treated with switching medications showed a mean BMI increase of 0.1 (p = 0.397); patients treated with combined medications showed a mean BMI increase of 0.5 (p = 0.208); and patients treated without medications showed a mean BMI increase of 0.1 (p = 0.821). The results indicated that patients with AN had a significant BMI increase after treatment with antidepressants and antipsychotics in the 6-month follow-up group. In Group B (12-month follow-up), patients treated with antidepressants showed a mean BMI increase of 2.7 (p < 0.001); patients treated with antipsychotics showed a mean BMI increase of 2.8 (p = 0.168); patients treated with switching medications showed a mean BMI decrease of 0.8 (p = 0.595); patients treated with combined medications showed a mean BMI increase of 1.6 (p = 0.368); and patients treated without medications showed a mean BMI increase of 1.0 (p = 0.262). The results indicated that patients with AN had a significant BMI increase after treatment with antidepressants at the 12-month follow-up. CONCLUSIONS: AN is a complex disease caused by multiple factors. Evaluating its long-term prognosis is crucial. Our study provides insights and highlights three key findings: 1) medication adherence is crucial in treating AN, 2) frequent switching of medications may not promote weight gain and may also require a re-establishment of rapport with patients with AN, and 3) pharmacotherapy, especially antidepressants, is more effective than no treatment. Further research is needed to confirm these findings.

Ketamine and Zinc: Treatment of Anorexia Nervosa Via Dual NMDA Receptor Modulation.

Anorexia nervosa is a disorder associated with serious adverse health outcomes, for which there is currently considerable treatment ineffectiveness. Characterised by restrictive eating behaviours, distorted body image perceptions and excessive physical activity, there is growing recognition anorexia nervosa is associated with underlying dysfunction in excitatory and inhibitory neurometabolite metabolism and signalling. This narrative review critically explores the role of N-methyl-D-aspartate receptor-mediated excitatory and inhibitory neurometabolite dysfunction in anorexia nervosa and its associated biomarkers. The existing magnetic resonance spectroscopy literature in anorexia nervosa is reviewed and we outline the brain region-specific neurometabolite changes that have been reported and their connection to anorexia nervosa psychopathology. Considering the proposed role of dysfunctional neurotransmission in anorexia nervosa, the potential utility of zinc supplementation and sub-anaesthetic doses of ketamine in normalising this is discussed with reference to previous research in anorexia nervosa and other neuropsychiatric conditions. The rationale for future research to investigate the combined use of low-dose ketamine and zinc supplementation to potentially extend the therapeutic benefits in anorexia nervosa is subsequently explored and promising biological markers for assessing and potentially predicting treatment response are outlined.

Individual differences in the positive outcome from adolescent ketamine treatment in a female mouse model of anorexia nervosa involve drebrin A at excitatory synapses of the medial prefrontal cortex.

Anorexia nervosa (AN) is a mental illness with the highest rates of mortality and relapse, and no approved pharmacological treatment. Using an animal model of AN, called activity-based anorexia (ABA), we showed earlier that a single intraperitoneal injection of ketamine at a dose of 30 mg/kg (30mgKET), but not 3 mg/kg (3mgKET), has a long-lasting effect upon adolescent females of ameliorating anorexia-like symptoms through the following changes: enhanced food consumption and body weight; reduced running and anxiety-like behavior. However, there were also individual differences in the drug's efficacy. We hypothesized that individual differences in ketamine's ameliorative effects involve drebrin A, an F-actin-binding protein known to be required for the activity-dependent trafficking of NMDA receptors (NMDARs). We tested this hypothesis by electron microscopic quantifications of drebrin A immunoreactivity at excitatory synapses of pyramidal neurons (PN) and GABAergic interneurons (GABA-IN) in deep layer 1 of prefrontal cortex (PFC) of these mice. Results reveal that (1) the areal density of excitatory synapses on GABA-IN is greater for the 30mgKET group than the 3mgKET group; (2) the proportion of drebrin A+ excitatory synapses is greater for both PN and GABA-IN of 30mgKET than 3mgKET group. Correlation analyses with behavioral measurements revealed that (3) 30mgKET's protection is associated with reduced levels of drebrin A in the cytoplasm of GABA-IN and higher levels at extrasynaptic membranous sites of PN and GABA-IN; (5) altogether pointing to 30mgKET-induced homeostatic plasticity that engages drebrin A at excitatory synapses of both PN and GABA-IN.