ArticleLiterature Review

A meta-analysis of inositol for depression and anxiety disorders

January 2014
Human Psychopharmacology Clinical and Experimental 29(1):55-63

Source
PubMed

Authors:

Fujita Health University

This study is a meta-analysis of inositol as a treatment for depression and anxiety disorders. PubMed, Cochrane Library database, and PsycINFO were searched up to 14 August 2013. A systematic review and meta-analysis of double-blind, randomized, placebo-controlled trials (RCTs) were conducted comparing inositol for depressed or anxiety disorder patients. Seven RCTs in depression (two bipolar depression studies, one bipolar depression and major depressive disorder (MDD) study, two MDD studies, and two premenstrual dysphoric disorder (PMDD) studies) (n = 242) were identified. Four RCTs in anxiety disorders (two obsessive-compulsive disorder studies, one panic disorder study, and one posttraumatic stress disorder study) (n = 70) were also identified. There were no statistically significant effects of inositol on depressive, anxiety, and obsessive-compulsive symptoms and discontinuation (all-cause, side effects, and worsening psychiatric symptoms). However, inositol had marginally more responders in depression than placebo (p = 0.06), and inositol showed a trend towards superior efficacy for depressive symptoms in patients with PMDD (p = 0.07). Inositol marginally caused gastrointestinal upset compared with placebo (p = 0.06). Our results suggest that inositol may be beneficial for depressed patients, especially those with PMDD. The main limitation of this report is that a small number of studies were included in this meta-analysis. Copyright © 2013 John Wiley & Sons, Ltd.

Current Trends, Challenges for Research, and Therapeutic Perspectives in Nutritional Psychiatry

Article

Mar 2024

"Nutritional interventions in the field of psychiatry have been explored more intensively in the last two decades, but definitive conclusions based on the retrieved data in the literature about the efficacy of this therapeutic approach are difficult to formulate. This observation has multiple explanations, e.g., these therapeutic interventions are very heterogenous, cohort studies usually enroll different psychiatric populations or healthy subjects with minor psychiatric symptoms, nutritional supplements or special diets are commonly recommended as add-ons to the pharmacological interventions (thus making it difficult to differentiate the impact of each therapy on the outcomes), placebo-controlled randomized studies are still very few, etc. Therefore, a narrative review focused on the main challenges reported during the research in the field of nutritional psychiatry (NP) may be useful for clinicians interested in strategies to augment the efficacy of pharmacological treatments or to find new solutions with low risk of adverse events in patients with organic comorbidities or multiple concomitant medications. Data about the efficacy and tolerability of nutritional interventions explored for psychiatric disorders were searched in four electronic databases (PubMed, Cochrane, Clarivate/Web of Science, and EMBASE). Omega-3 polyunsaturated fatty acids supplementation, healthy diet interventions, folate and vitamin B12, S-adenosyl-L-methionine, N-acetyl cysteine, vitamin B1 and B6, vitamin D, minerals, psychobiotics, inositol, and herbal products were the main interventions identified, and their demonstrated efficacy was quite heterogenous, while their tolerability and safety were good. Therefore, NP is a domain of research that may benefit from more good-quality and longer-duration trials, in order to verify the effectiveness of such augmentation strategies to the already validated treatments."

Neurobiology and Applications of Inositol in Psychiatry: A Narrative Review

Article

Full-text available

Feb 2023
CURR ISSUES MOL BIOL

Inositol is a natural sugar-like compound, commonly present in many plants and foods. It is involved in several biochemical pathways, most of them controlling vital cellular mechanisms, such as cell development, signaling and nuclear processes, metabolic and endocrine modulation, cell growth, signal transduction, etc. In this narrative review, we focused on the role of inositol in human brain physiology and pathology, with the aim of providing an update on both potential applications and current limits in its use in psychiatric disorders. Overall, imaging and biomolecular studies have shown the role of inositol levels in the pathogenesis of mood disorders. However, when administered as monotherapy or in addition to conventional drugs, inositol did not seem to influence clinical outcomes in both mood and psychotic disorders. Conversely, more encouraging results have emerged for the treatment of panic disorders. We concluded that, despite its multifaceted neurobiological activities and some positive findings, to date, data on the efficacy of inositol in the treatment of psychiatric disorders are still controversial, partly due to the heterogeneity of supporting studies. Therefore, systematic use of inositol in routine clinical practice cannot be recommended yet, although further basic and translational research should be encouraged.

Repurposed drugs as adjunctive treatments for mania and bipolar depression: A meta-review and critical appraisal of meta-analyses of randomized placebo-controlled trials

Article

Sep 2021
J PSYCHIATR RES

Several drugs previously tested in clinical trials and approved for different indications have been repurposed for bipolar disorder. We carried out a systematic meta-review of meta-analyses of randomized placebo-controlled trials investigating repurposed drugs as adjunctive treatments for mania and bipolar depression. We performed a critical appraisal using ‘A MeaSurement Tool to Assess systematic Reviews’ Version 2 (AMSTAR 2). We synthesized results on efficacy, tolerability, and safety, assessing evidence quality according to the ‘Grading of Recommendations, Assessment, Development and Evaluations’ (GRADE) approach. Our systematic search identified nine eligible studies investigating 12 drugs, four for mania and eight for bipolar depression. The quality of reporting was heterogeneous according to AMSTAR 2. In mania, allopurinol (for symptoms reduction and remission at 4–8 weeks) and tamoxifen (for response and symptoms reduction at 4–6 weeks) showed higher efficacy than placebo, with low and very low quality of evidence, respectively. Concerning bipolar depression, modafinil/armodafinil (for response, remission, and symptoms reduction at 6–8 weeks) and pramipexole (for response and symptoms reduction at 6 weeks) were superior to placebo, despite the low quality of evidence. Results on the efficacy of celecoxib and N-acetylcysteine were of low quality and limited to certain outcomes. Overall, the lack of evidence of high and moderate quality does not allow us to draw firm conclusions on the clinical utility of repurposed drugs as adjunctive treatments for mania and bipolar depression, highlighting the need for additional research.

The efficacy and safety of nutrient supplements in the treatment of mental disorders: a meta-review of meta-analyses of randomized controlled trials

Article

Full-text available

Sep 2019

The role of nutrition in mental health is becoming increasingly acknowledged. Along with dietary intake, nutrition can also be obtained from “nutrient supplements”, such as polyunsaturated fatty acids (PUFAs), vitamins, minerals, antioxidants, amino acids and pre/probiotic supplements. Recently, a large number of meta‐analyses have emerged examining nutrient supplements in the treatment of mental disorders. To produce a meta‐review of this top‐tier evidence, we identified, synthesized and appraised all meta‐analyses of randomized controlled trials (RCTs) reporting on the efficacy and safety of nutrient supplements in common and severe mental disorders. Our systematic search identified 33 meta‐analyses of placebo‐controlled RCTs, with primary analyses including outcome data from 10,951 individuals. The strongest evidence was found for PUFAs (particularly as eicosapentaenoic acid) as an adjunctive treatment for depression. More nascent evidence suggested that PUFAs may also be beneficial for attention‐deficit/hyperactivity disorder, whereas there was no evidence for schizophrenia. Folate‐based supplements were widely researched as adjunctive treatments for depression and schizophrenia, with positive effects from RCTs of high‐dose methylfolate in major depressive disorder. There was emergent evidence for N‐acetylcysteine as a useful adjunctive treatment in mood disorders and schizophrenia. All nutrient supplements had good safety profiles, with no evidence of serious adverse effects or contraindications with psychiatric medications. In conclusion, clinicians should be informed of the nutrient supplements with established efficacy for certain conditions (such as eicosapentaenoic acid in depression), but also made aware of those currently lacking evidentiary support. Future research should aim to determine which individuals may benefit most from evidence‐based supplements, to further elucidate the underlying mechanisms.

Myo-Inositol and Its Derivatives: Their Roles in the Challenges of Infertility

Article

Full-text available

Nov 2024

Myo-inositol (MYO) and D-chiro-inositol (DCI) are the two most significant isomeric forms of inositol, playing a critical role in intracellular signaling. MYO is the most abundant form of inositol in nature; DCI is produced from MYO through epimerization by an insulin-dependent enzyme. Recently, it has been demonstrated that inositol may influence oocyte maturation and improve intracellular Ca²⁺ oscillation in the oocytes, and it has been proposed as a potential intervention for restoring spontaneous ovulation. The MYO concentration in human follicular fluid is considered a bioindicator of oocyte quality. In the ovary, DCI modulates the activity of aromatase, thus regulating androgen synthesis. Under physiological conditions, the MYO/DCI ratio is maintained at 40:1 in plasma. In women with PCOS, the MYO/DCI ratio is lowered to 0:2:1, contributing to elevated androgen production. By regulating FSH signaling, MYO administration increases the number of high-quality embryos available for transfer in poor responder patients. Finally, by acting downstream to insulin signaling, inositol administration during pregnancy may represent a novel strategy for counteracting gestational diabetes. These findings show that diet supplementation with inositol may be a promising strategy to address female infertility and sustain a healthy pregnancy.

Myo-Inositol and Its Derivatives: Their Role in the Challenges of Infertility

Preprint

Full-text available

Oct 2024

Myo-inositol (MYO) and D-chiro-inositol (DCI) are the two most significant isomeric forms of inositol, playing a critical role in intracellular signaling. MYO is the most abundant form of inositol in nature; DCI is produced from MYO through epimerization by an insulin-dependent enzyme. Recently, it has been demonstrated that inositols may influence oocyte maturation, improve intracellular Ca2+ oscillation in the oocytes and have been proposed as potential interventions for restoring spontaneous ovulation. MYO concentration in human follicular fluid is considered a bioindicator of oocyte quality. In the ovary, DCI modulates the activity of aromatase thus regulating androgen synthesis. Under physiological conditions, MYO/DCI ratio is maintained at 40:1 in the plasma. In women with PCOS, MYO/DCI ratio lowers to 0:2:1, contributing to elevated androgen production. By regulating FSH signaling, MYO administration increases the number of high-quality embryos available for transfer in poor responder patients. Finally, by acting downstream to insulin signaling inositol administration during pregnancy may represent a novel strategy for counteracting gestational diabetes. These findings show that diet supplementation with inositols may be a promising strategy to address female infertility and sustain healthy pregnancy.

Inositol for the Prevention of Neural Tube Defects: A Potential Opportunity for Advocacy in Global Pediatric Neurosurgery

Article

Sep 2022

Objetivo: Aproximadamente el 70-80% de los defectos del tubo neural (DTN) responden al folato. El mioinositol se ha identificado cada vez más como una posible solución para tratar los defectos del tubo neural que no responden al folato. Brindamos una breve reseña de la evidencia existente sobre el papel del mioinositol en la prevención de los NTD y describimos su papel en los esfuerzos de promoción centrados en la prevención de los NTD. Métodos: Se realizó una revisión narrativa. Resultados:Los datos existentes sobre la eficacia de la suplementación con inositol están limitados por los tamaños de muestra bajos y los diseños de estudio principalmente observacionales. Aunque los esfuerzos de promoción con respecto a las NTD se han centrado en la fortificación y la suplementación con folato, vale la pena examinar los datos sobre la ingesta de inositol. Después de revisar los datos, planteamos que sería necesario cumplir una serie de criterios incluso antes de considerar la promoción y la política. Primero, el peso de la evidencia debe favorecer el aumento de la ingesta de inositol. En segundo lugar, debe demostrarse la rentabilidad de la política de inositol. Tercero, la política debe ser políticamente viable. En cuarto lugar, se debe generar prioridad política para la política. En quinto lugar, se debe generar una sinergia entre los esfuerzos de política de folato existentes y los esfuerzos de política de inositol. Después de examinar esa serie de criterios, Conclusión: el inositol puede representar una vía para reducir la prevalencia de nacimientos de defectos del tubo neural que no responden al folato. Dadas sus funciones clínicas en el tratamiento de la espina bífida y los defectos del tubo neural, los neurocirujanos también son fundamentales para los esfuerzos de promoción en la prevención.

The forced swim test has poor accuracy for identifying novel antidepressants

Article

Aug 2021

Despite the prevalence of treatment-resistant depression, many pharmaceutical companies have abandoned the development of new antidepressants. Experts have attributed this, in part, to the low quality of preclinical tests available in this field, often citing over-reliance on animal behavioral screens, such as the forced swim test (FST). This retrospective review assessed whether compounds tested in the FST by major pharmaceutical companies were shown to have antidepressant effects in humans. Of 109 compounds identified, only 28% had been explored for antidepressant effects in humans. Of these, there were only three for which the FST appeared to positively predict antidepressant efficacy, but none are currently approved to treat any type of depression. With such poor accuracy for identifying novel antidepressants, the FST might not be a useful screening tool for this purpose.

Paper Cantelmi (1) (1) (1)

Article

Full-text available

Mar 2021
EUR REV MED PHARMACO

OBJECTIVE: PCOS women experience different discomfort as a consequence of the illness. During the years, several risk factors and treatments emerged. This review aims at underlining evidence on psychological symptoms in PCOS women and on the effectiveness of therapies. MATERIALS AND METHODS: We reviewed literature searching through different databases. We used different keywords, including: PCOS, PCOS and depression, PCOS and anxiety , PCOS and psychological, PCOS depression and risk factors, PCOS depression therapies, depression and inositol. RESULTS: Based on the collected evidence, PCOS women are more likely to develop psychological symptoms, like depression or anxiety disorders. Furthermore, several risk factors are associated with higher depression or worse psychological conditions. Particularly, the literature highlights BMI, hirsutism, insulin resistance, excess of androgens and lack of serum Vitamin D. Even though several pharmaceuticals find application in psychological symptoms, some of them can impair hormonal condition in PCOS women. Few molecules are able to improve psychological symptoms without impairing hormonal profiles. Among these, myo-inositol appears to be the most interesting, as it is also considered first-line therapy in PCOS women. CONCLUSIONS: Psychological symptoms affect PCOS women more than healthy subjects. Among the different treatments, inositol emerges as a safe approach, being the first-line therapy in PCOS for hormonal improvement and having putative effects also in psychiatrists.

Inositol treatment for psychological symptoms in Polycystic Ovary Syndrome women

Article

Full-text available

Mar 2021

Objective: PCOS women experience different discomfort as a consequence of the illness. During the years, several risk factors and treatments emerged. This review aims at underlining evidence on psychological symptoms in PCOS women and on the effectiveness of therapies. Materials and methods: We reviewed literature searching through different databases. We used different keywords, including: PCOS, PCOS and depression, PCOS and anxiety, PCOS and psychological, PCOS depression and risk factors, PCOS depression therapies, depression and inositol. Results: Based on the collected evidence, PCOS women are more likely to develop psychological symptoms, like depression or anxiety disorders. Furthermore, several risk factors are associated with higher depression or worse psychological conditions. Particularly, the literature highlights BMI, hirsutism, insulin resistance, excess of androgens and lack of serum Vitamin D. Even though several pharmaceuticals find application in psychological symptoms, some of them can impair hormonal condition in PCOS women. Few molecules are able to improve psychological symptoms without impairing hormonal profiles. Among these, myo-inositol appears to be the most interesting, as it is also considered first-line therapy in PCOS women. Conclusions: Psychological symptoms affect PCOS women more than healthy subjects. Among the different treatments, inositol emerges as a safe approach, being the first-line therapy in PCOS for hormonal improvement and having putative effects also in psychiatrists.

Inositols and metabolic disorders: From farm to bedside

Article

Full-text available

Mar 2020

Inositol and its derivates are catching interest in metabolism since taking part in several physiological processes, including endocrine modulation. Through several mechanisms mostly mediated by insulin signaling, these compounds regulate the activities of several hormones and are essential in oocytes maturation. It is interesting to point out the contribution of an inositol deficiency in the development of several diseases, mainly in the metabolic and endocrine setting. Inositols derive from both diet and endogenous production; among causes of inositol deficiency reduced dietary intake, increased catabolism and/or excretion, decreased biosynthesis, inhibition of gut and cellular uptake and altered microbiota could be considered. Mounting direct and indirect evidence suggests that the two main isoforms (Myo-inositol-inositol, D-chiro-inositol) are implied in glycemic and lipidic metabolism and supplementation yield a beneficial effect on these parameters without hazards for health. Moreover, they have a role in polycystic ovary syndrome, acting as insulin-sensitizing agents and free radical scavengers, helping to regulate metabolism and promoting ovulation. The aim of this narrative review is to discuss the role of inositols in metabolic function disorders paying attention to whether these compounds could be efficacious and safe as a therapeutic agent with a focus on dietary intake and the role of gut microbiota.

Inositol – multidimensional support for metabolic and mental health

Article

Feb 2025

Inositol Phosphates and Synthesizing Enzymes: Implications in Neurodegenerative Disorders

Article

Full-text available

Feb 2025

Inositol is a vital sugar molecule involved in numerous signaling pathways required for cellular homeostasis and cell survival. Myo-inositol and its phospho-derivatives, inositol phosphates (IPs), are the most prevalent forms of inositol found in living cells. They are involved in regulating ion channels, metabolic flux, stress response, and other key biological processes. While emerging research has highlighted the significant roles of inositol phosphates in immunity, cancer, and metabolic diseases, there is a lack of comprehensive reviews on their roles in psychiatric and neurological disorders. This review aims to fill that gap by analyzing the existing literature on the importance of inositol phosphates in severe psychiatric and neurological conditions such as Parkinson’s disease, Alzheimer’s disease, bipolar disorder, amyotrophic lateral sclerosis, schizophrenia, and Huntington’s disease, underscoring the potential to pave the way for new treatment regimens for these debilitating disorders targeting inositol pathways.

Exploring the potential of myo-inositol in thyroid disease management: focus on thyroid cancer diagnosis and therapy

Article

Full-text available

Sep 2024

Thyroid cancer (TC) is a malignancy that is increasing in prevalence on a global scale, necessitating the development of innovative approaches for both diagnosis and treatment. Myo-inositol (MI) plays a crucial role in a wide range of physiological and pathological functions within human cells. To date, studies have investigated the function of MI in thyroid physiology as well as its potential therapeutic benefits for hypothyroidism and autoimmune thyroiditis. However, research in the field of TC is very restricted. Metabolomics studies have highlighted the promising diagnostic capabilities of MI, recognizing it as a metabolic biomarker for identifying thyroid tumors. Furthermore, MI can influence therapeutic characteristics by modulating key cellular pathways involved in TC. This review evaluates the potential application of MI as a naturally occurring compound in the management of thyroid diseases, including hypothyroidism, autoimmune thyroiditis, and especially TC. The limited number of studies conducted in the field of TC emphasizes the critical need for future research to comprehend the multifaceted role of MI in TC. A significant amount of research and clinical trials is necessary to understand the role of MI in the pathology of TC, its diagnostic and therapeutic potential, and to pave the way for personalized medicine strategies in managing this intricate disease.

Update on the combination of myo-inositol/d-chiro-inositol for the treatment of polycystic ovary syndrome

Article

Full-text available

Jan 2024

In this article, we present a narrative review on the use of inositol in the treatment of polycystic ovary syndrome (PCOS). Of the different inositols that exist, only myo-inositol (MYO) and D-chiro inositol (DCI) have been studied in the treatment of PCOS. The results of the studies show that there is insufficient or controversial evidence to recommend the use of DCI alone, while MYO alone shows positive results and, above all, the MYO/DCI combination is effective when used at a ratio of at least 40:1, but there is enough rationale to further study ratios such as 66:1 to 100:1 as other possible effective combinations.

Management of Premenstrual Dysphoric Disorder: A Scoping Review

Article

Jan 2024

Possible prospects for the combined administration of antidepressants and antioxidants in neurological patients

Article

Nov 2023

Antidepressants (ADs) are a group of drugs whose action primarily consists of stimulating neurotransmitter systems (dopaminergic, serotonergic and noradrenergic systems). Neurologists prescribe them for the treatment of post-stroke and other depression, chronic pain syndromes, neuropathic pain, panic attacks, correction of post-Covid syndrome, for the prevention of migraines, Parkinson’s disease and neurodegenerative diseases, including Alzheimer’s disease. However, even with appropriate therapy, many people with depressive disorder may experience subsyndromal symptoms and complete remission is short-lived, so there is a need to use other therapeutic approaches. Combining two or more antidepressants may target different neurochemical pathways while increasing the risk of side effects and the development of resistance. Therefore, the search for alternative treatments is urgent, and oxidative stress appears to be an interesting therapeutic target. The combined use of AD and antioxidants may provide an effective and safe approach to enhancing antidepressant effects by synergistically enhancing certain antidepressant activities (eg, enhancing monoamine reuptake inhibition) or by additive pharmacological effects, such as adjusting neurotransmitters and reducing the damaging effects of active agents. forms of oxygen. There are a number of clinical studies to prove the effectiveness of the combined use of antioxidants and antioxidants. In the group of patients receiving a combination of antioxidants and antidepressants/anti-anxiety drugs, there was a better regression of symptoms and severity of depression, which probably indicates the usefulness of adjuvant antioxidant therapy with regular psychotropic treatment. The use of combination drugs in complex therapy with blood pressure seems to be a promising direction and requires further study.

Chronic inflammation, neuroglia dysfunction, and plasmalogen deficiency as a new pathobiological hypothesis addressing the overlap between post-COVID-19 symptoms and myalgic encephalomyelitis/chronic fatigue syndrome

Article

Full-text available

Jul 2023
BRAIN RES BULL

After five waves of COVID-19 outbreaks, it has been recognized that a significant portion of the affected individuals developed long-term debilitating symptoms marked by chronic fatigue, cognitive difficulties ("brain fog"), post-exertional malaise, and autonomic dysfunction. The onset, progression, and clinical presentation of this condition, generically named post-COVID-19 syndrome, overlap significantly with another enigmatic condition, referred to as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Several pathobiological mechanisms have been proposed for ME/CFS, including redox imbalance, systemic and central nervous system inflammation, and mitochondrial dysfunction. Chronic inflammation and glial pathological reactivity are common hallmarks of several neurodegenerative and neuropsychiatric disorders and have been consistently associated with reduced central and peripheral levels of plasmalogens, one of the major phospholipid components of cell membranes with several homeostatic functions. Of great interest, recent evidence revealed a significant reduction of plasmalogens contents, biosynthesis, and metabolism in ME/CFS and acute COVID-19, with a strong association to symptom severity and other relevant clinical outcomes. These bioactive lipids have increasingly attracted attention due to their reduced levels representing a common pathophysiological manifestation between several disorders associated with aging and chronic inflammation. However, alterations in plasmalogen levels or their lipidic metabolism have not yet been examined in individuals suffering from post-COVID-19 symptoms. Here, we proposed a pathobiological model for post-COVID-19 and ME/CFS based on their common inflammation and dysfunctional glial reactivity, and highlighted the emerging implications of plasmalogen deficiency in the underlying mechanisms. Along with the promising outcomes of plasmalogen replacement therapy (PRT) for various neurodegenerative/neuropsychiatric disorders, we sought to propose PRT as a simple, effective, and safe strategy for the potential relief of the debilitating symptoms associated with ME/CFS and post-COVID-19 syndrome.

Electroconvulsive therapy triggers a reversible decrease in brain N-acetylaspartate

Article

Full-text available

Jun 2023

Introduction Based on previous research on electroconvulsive therapy (ECT) we have proposed a model where disruption, potentiation, and rewiring of brain networks occur in sequence and serve as the underlying therapeutic mechanism of ECT. This model implies that a temporary disturbance of neuronal networks (disruption) is followed by a trophic effect (potentiation), which enables the rewiring of neuronal circuits to a more euthymic functioning brain. We hypothesized that disruption of neuronal networks could trigger biochemical alterations leading to a temporary decrease in N-acetylaspartate (tNAA, considered a marker of neuronal integrity), while choline (a membrane component), myo-Inositol (mI, astroglia marker), and glutamate/glutamine (Glx, excitatory neurotransmitter) were postulated to increase. Previous magnetic resonance spectroscopy studies, reporting diverse findings, have used two different referencing methods - creatine ratios and tissue corrected values referenced to water – for the quantification of brain metabolites. Changes in creatine during ECT have also been reported, which may confound estimates adopting this as an internal reference. Methods Using MR spectroscopy, we investigated 31 moderately to severely depressed patients and 19 healthy controls before, during, and after ECT or at similar time points (for controls). We tested whether biochemical alterations in tNAA, choline, mI, and Glx lend support to the disrupt, potentiate, and rewire hypothesis. We used both creatine ratios and water-scaled values for the quantification of brain metabolites to validate the results across referencing methods. Results Levels of tNAA in the anterior cingulate cortex decreased after an ECT treatment series (average 10.6 sessions) by 6% (p = 0.007, creatine ratio) and 3% (p = 0.02, water referenced) but returned to baseline 6 months after ECT. Compared to after treatment series tNAA levels at 6-month follow-up had increased in both creatine ratio (+6%, p < 0.001) and water referenced data (+7%, p < 0.001). Findings for other brain metabolites varied and could not be validated across referencing methods. Discussion Our findings suggest that prior research must be interpreted with care, as several referencing and processing methods have been used in the past. Yet, the results for tNAA were robust across quantification methods and concur with relevant parts of the disrupt, potentiate, and rewire model.

Sexual Function and Depressive Symptoms in Young Women with Euthyroid Hashimoto’s Thyroiditis Receiving Vitamin D, Selenomethionine and Myo-Inositol: A Pilot Study

Article

Full-text available

Jun 2023

Thyroid autoimmunity is associated with an increased risk of sexual dysfunction. The aim of this study was to compare sexual functioning and depressive symptoms in women with Hashimoto’s thyroiditis receiving different treatments. The study included euthyroid women with autoimmune thyroiditis, untreated or receiving vitamin D, selenomethionine, or myo-inositol. Apart from measuring antibody titers and hormone levels, all participants completed questionnaires evaluating female sexual function (FSFI) and depressive symptoms (BDI-II). In untreated women, the overall FSFI scores and domain scores for desire, arousal, lubrication, and sexual satisfaction were lower than in women receiving vitamin D, selenomethionine, and myo-inositol. In the vitamin D-treated women, the total FSFI scores and scores for desire and arousal were higher than in women receiving the remaining micronutrients. The BDI-II score was lowest in the vitamin D-treated women and highest in the untreated patients with thyroiditis. Vitamin D-treated women were also characterized by lower antibody titers and higher testosterone levels than the women receiving the remaining micronutrients. There were no differences in sexual functioning and depressive symptoms between the selenomethionine- and myo-inositol-treated women. The study results suggest that although all antibody-lowering treatments are associated with better sexual functioning and well-being in young women with euthyroid autoimmune thyroiditis, the greatest benefits are observed in patients receiving vitamin D.

Antiepileptic Properties of Scyllo-Inositol on Pentylenetetrazol-Induced Seizures

Article

Full-text available

Apr 2023
INT J MOL SCI

Epilepsy, with about 70 million affected people worldwide, is one of the biggest challenges of medicine today. It is estimated that about one-third of epileptic patients receive inadequate treatment. Inositols have proved effective in many disorders; hence, in the current study, we tested potential antiepileptic properties of scyllo-inositol (SCI)—one of the most common commercially available inositols—in zebrafish larvae with pentylenetetrazol-induced seizures. First, we studied the general effect of SCI on zebrafish motility, and then we tested SCI antiepileptic properties over short (1 h) and long (120 h) exposure protocols. Our results demonstrated that SCI alone does not reduce zebrafish motility regardless of the dose. We also observed that short-term exposure to SCI groups reduced PTZ-treated larva motility compared to controls (p < 0.05). In contrast, prolonged exposure did not produce similar results, likely due to the insufficient concentration of SCI given. Our results highlight the potential of SCI use in epilepsy treatment and warrant further clinical studies with inositols as potential seizure-reducing drugs.

Management of Premenstrual Dysphoric Disorder: A Scoping Review

Article

Full-text available

Dec 2022

Premenstrual dysphoric disorder (PMDD) and premenstrual syndrome (PMS) refer to physical, cognitive, or affective symptoms that arise in the late luteal phase and remit with menses. The present work is a clinically focused scoping review of the last twenty years of research on treatment for these disorders. A search of key terms using the PubMed/Medline, the Cochrane Library, Embase, and Web of Science databases was performed, and 194 studies of adult women met initial inclusion criteria for review. Research studies concerning medications, pharmacological and non-pharmacological complementary and alternative medicine treatments, and surgical interventions with the most available evidence were appraised and summarized. The most high-quality evidence can be found for the use of selective serotonin reuptake inhibitors (SSRIs) and combined oral contraceptives (COCs), with gonadotropin releasing hormone (GnRH) agonists and surgical interventions showing efficacy for refractory cases. While there is some evidence of the efficacy of alternative and complementary medicine treatments such as nutraceuticals, acupuncture, and yoga, variability in quality and methods of studies must be taken into account.

Mitochondrial modulators for obsessive–compulsive and related disorders: a systematic review and meta-analysis

Article

Full-text available

Jun 2022

It remains unclear whether mitochondrial modulators (MMs) are beneficial in the treatment of obsessive–compulsive and related disorders. Thus, in an attempt to answer this clinical question, we performed a systematic review and a random-effects meta-analysis of double-blind, randomized, placebo-controlled trials. The primary outcome was change in overall symptoms as measured using standardized rating scales. Other outcomes were response to treatment; improvement in anxiety-related scales scores, depression-related scale scores, Clinical Global Impression Severity Scale (CGI-S) scores, and Sheehan Disability Scale (SDS) scores; all-cause discontinuation; and individual adverse events. We calculated the standardized mean differences for continuous outcomes and risk ratios for dichotomous outcomes with 95% confidence intervals. We reviewed 17 studies (n = 629, 72.62% female; duration = 2–20 weeks; mean age = 30.47 years) of MMs: eicosapentaenoic acid (K = 1), folic acid (K = 1), lithium (K = 1), N-acetylcysteine (K = 10), inositol (K = 3), and silymarin (K = 1). MMs outperformed placebo in overall improvement in symptoms (p < 0.01) and in improving anxiety-related scale scores (p = 0.05). Subgroup analysis of individual MMs revealed that although overall symptoms were better improved by N-acetylcysteine (p < 0.01) and lithium (p = 0.04), no MMs outperformed placebo in terms of improving anxiety-related scale scores. Neither pooled nor individual MMs outperformed placebo in improving response to treatment, depression-related scale scores, CGI-S scores, SDS scores, or all-cause discontinuation. N-acetylcysteine was no more associated with a higher incidence of individual adverse events including gastrointestinal symptoms, than placebo. In conclusion, N-acetylcysteine was beneficial in the treatment of obsessive–compulsive and related disorders. However, further study with larger samples is necessary to confirm this finding.

Gut Microbiota and Depressive Symptoms at the End of CRT for Rectal Cancer: A Cross-Sectional Pilot Study

Article

Full-text available

Dec 2021
Depress Res Treat

Background: The role of alterations in gut microbiota composition (termed dysbiosis) has been implicated in the pathobiology of depressive symptoms; however, evidence remains limited. This cross-sectional pilot study is aimed at exploring whether depressive symptom scores changed during neoadjuvant chemotherapy and radiation therapy to treat rectal cancer, and if gut microbial taxa abundances and predicted functional pathways correlate with depressive symptoms at the end of chemotherapy and radiation therapy. Methods: 40 newly diagnosed rectal cancer patients (ages 28-81; 23 males) were assessed for depressive symptoms using the Hamilton Rating Scale for Depression (HAM-D) and provided stool samples for 16S rRNA sequencing. Gut microbiome data were analyzed using QIIME2, and correlations and regression analyses were performed in R. Results: Participants had significantly higher depressive symptoms at the end as compared to before CRT. The relative abundances of Gemella, Bacillales Family XI, Actinomyces, Streptococcus, Lactococcus, Weissella, and Leuconostocaceae were positively correlated (Spearman's rho = 0.42 to 0.32), while Coprobacter, Intestinibacter, Intestimonas, Lachnospiraceae, Phascolarctobacterium, Ruminiclostridium, Ruminococcaceae (UCG-005 and uncultured), Tyzzerella, and Parasutterella (Spearman's rho = -0.43 to - 0.31) were negatively correlated with HAM-D scores. Of the 14 predicted MetaCyc pathways that correlated with depressive symptom scores at the end of CRT, 11 (79%) were associated with biosynthetic pathways. Conclusions: Significant bacterial taxa and predicted functional pathways correlated with depressive symptoms at the end of chemotherapy and radiation therapy for rectal cancer which warrants further examination and replication of our findings.

Minority Stress and the Effects on Emotion Processing in Transgender Men and Cisgender People: A Study Combining fMRI and Proton Magnetic Resonance Spectroscopy (1H-MRS)

Article

Full-text available

Dec 2021
INT J NEUROPSYCHOPH

Abstract Background Minority stress via discrimination, stigmatization, and exposure to violence can lead to development of mood and anxiety disorders and underlying neurobiochemical changes. To date, the neural and neurochemical correlates of emotion processing in transgender people (and their interaction) are unknown. Methods This study combined functional magnetic resonance imaging (fMRI) and magnetic resonance spectroscopy ( 1H-MRS) to uncover the effects of anxiety and perceived stress on the neural and neurochemical substrates, specifically Choline, on emotion processing in transgender men. Thirty transgender men (TM), 30 cisgender men (CM), and 35 cisgender women (CW) passively viewed angry, neutral, happy, and surprise faces in the fMRI scanner, underwent a 1H-MRS scan and filled out mood and anxiety related questionnaires. Results As predicted, Choline levels modulated the relationship between anxiety and stress symptoms and the neural response to angry and surprise (but not happy faces) in the amygdala. This was only the case for TM but not cisgender comparisons. More generally, neural responses in the left amygdala, left middle frontal gyrus, and medial frontal gyrus to emotional faces in TM resembled that of CW. Conclusions These results provide first evidence of a critical interaction between levels of analysis and that Choline may influence neural processing of emotion in individuals prone to minority stress.

Role of Inositols and Inositol Phosphates in Energy Metabolism

Article

Full-text available

Nov 2020
MOLECULES

Recently, inositols, especially myo-inositol and inositol hexakisphosphate, also known as phytic acid or IP6, with their biological activities received much attention for their role in multiple health beneficial effects. Although their roles in cancer treatment and prevention have been extensively reported, interestingly, they may also have distinctive properties in energy metabolism and metabolic disorders. We review inositols and inositol phosphate metabolism in mammalian cells to establish their biological activities and highlight their potential roles in energy metabolism. These molecules are known to decrease insulin resistance, increase insulin sensitivity, and have diverse properties with importance from cell signaling to metabolism. Evidence showed that inositol phosphates might enhance the browning of white adipocytes and directly improve insulin sensitivity through adipocytes. In addition, inositol pyrophosphates containing high-energy phosphate bonds are considered in increasing cellular energetics. Despite all recent advances, many aspects of the bioactivity of inositol phosphates are still not clear, especially their effects on insulin resistance and alteration of metabolism, so more research is needed.

The Role of Diet, Eating Behavior, and Nutrition Intervention in Seasonal Affective Disorder: A Systematic Review

Article

Full-text available

Aug 2020

Background: Seasonal affective disorder (SAD) is a biological and mood disorder with a seasonal pattern. Dietary intervention and nutritional status have been reported to affect SAD severity. The objective of this study was to systematically review the evidence of associations between SAD and diet, eating behavior, and nutrition intervention. Methods: We performed a comprehensive search of MEDLINE, EMBASE, Web of Science, and Google Scholar from inception up to July 1, 2019. Studies that examined diet and eating behaviors in SAD patients and tests of nutrition interventions for SAD were included. Two independent investigators extracted data based on study designs, participants, outcomes, exposures, and association measures. Results: Eleven studies were included: six studies examined distinctive dietary patterns and eating behaviors in SAD patients and five studies explored the efficacy of nutrition interventions for SAD. Vegetarianism and alcoholism were associated with higher SAD prevalence, but normal alcohol intake was not correlated with SAD severity. Compared with non-clinical subjects, SAD patients tended to consume significantly larger dinners and more evening snacks during weekdays and weekends and exhibit a higher frequency of binge eating, external eating, and emotional eating. Additionally, compared to healthy controls, SAD patients presented more cravings for starch-rich food and food with high fiber. However, neither the ingestion of carbohydrate-loaded meals nor Vitamin D/B12 supplementation showed benefit for SAD. Conclusion: Studies suggest that SAD patients may exhibit distinctive diet preferences and eating behaviors, but no current nutrition intervention has demonstrated efficacy for ameliorating SAD symptoms. Further evidence is needed from randomized controlled trials with larger sample sizes and longer durations.

Analysis of genetic differences between psychiatric disorders: exploring pathways and cell-types/tissues involved and the ability to distinguish the disorders by polygenic scores

Preprint

Full-text available

Mar 2020

Psychiatric disorders are common and are among the top causes disabilities around the world. On the other hand, although displaying strong genetic correlations, these disorders have been clinically defined as independent categorical entities as they each have some distinguishing clinical symptoms and may involve different treatments. Identifying differential genetic variations between these disorders may shed light on how the disorders differ biologically and help to guide more personalized treatment in the future. Another potential clinical application is differentiating different disorders by genetic markers. For example, a patient who presents with depression may actually be having bipolar disorder (BPD). Here we presented a comprehensive analysis to identify genetic markers differentially associated for various psychiatric disorders based on GWAS summary statistics. We performed comparisons among schizophrenia (SCZ), bipolar disorder (BPD), major depressive disorder (MDD) as well as six other pairs of genetically related psychiatric disorders/traits. Importantly, we also conducted comprehensive computational analysis to unravel the genes, pathways and SNP functional categories involved, and unravelled the most relevant cell types and tissues for differentiating the disorders. We also uncovered differences in each studied pair of disorders in terms of their differences in comorbid traits, using LD score regression. Another novel contribution is that we assessed how well we could distinguish two psychiatric disorders (e,g, MDD vs BPD) by the use of polygenic risk scores (PRS). This may be clinically relevant in the future given the lack of biomarkers to aid differential diagnosis of psychiatric disorder.

Myo-inositol: its metabolism and potential implications for poultry nutrition—a review

Article

Full-text available

Feb 2020

Myo-inositol (MI) has gained relevance in physiology research during the last decade. As a constituent of animal cells, MI was proven to be crucial in several metabolic and regulatory processes. Myo-inositol is involved in lipid signaling, osmolarity, glucose, and insulin metabolism. In humans and rodents, dietary MI was assessed to be important for health so that MI supplementation appeared to be a valuable alternative for treatment of several diseases as well as for improvements in metabolic performance. In poultry, there is a lack of evidence not only related to specific species-linked metabolic processes but also about the effects of dietary MI on performance and health. This review intends to provide information about the meaning of dietary MI in animal metabolism as well as to discuss potential implications of dietary MI in poultry health and performance with the aim to identify open questions in poultry research.

The CINP guidelines on the definition and the evidence-based interventions for treatment-resistant Bipolar disorder

Article

Full-text available

Dec 2019
INT J NEUROPSYCHOPH

Introduction: Resistant Bipolar disorder (BD) is a major mental health problem related to significant disability and overall cost. The aim of the current study was to perform a systematic review of the literature concerning a) the definition of treatment resistance in BD, b) its clinical and c) neurobiological correlates, and d) the evidence-based treatment options for treatment resistant BD and eventually to develop guidelines for the treatment of this condition. Material and methods: The PRISMA method was used to identify all published papers relevant to the definition of treatment resistance in BD and the associated evidence-based treatment options. The MEDLINE was searched to April 22nd, 2018. Results: Criteria were developed for the identification of resistance in BD concerning all phases. The search of the literature identified all published studies concerning treatment options. The data were classified according to strength and separate guidelines concerning resistant acute mania, acute bipolar depression and the maintenance phase were developed. Discussion: The definition of resistance in BD is by itself difficult due to the complexity of the clinical picture, course and treatment options. The current guidelines are the first developed specifically for the treatment of resistant BD patients and they also include an operationalized definition of treatment resistance. They were based on a thorough and deep search of the literature.and utilize as much as possible an evidence-based approach.

Treatment for Depression Among Adults: An Evidence and Gap Map of Systematic Reviews

Article

Full-text available

Mar 2025

Objective To identify and map systematic reviews on the effectiveness of treatment for depressive disorders among adults. Methods We retrieved systematic reviews and meta‐analyses of randomized controlled trials involving adults with depressive symptoms from twelve English and four Chinese databases (June 21, 2022). Using an interactive map, we visualized the effectiveness of evidence on depression based on an intervention‐outcome framework. The interventions included psychotherapy, pharmacotherapy, complementary and alternative treatments, and others. The outcomes included the remission of depressive symptoms, symptoms of depressive disorder, life and social skills, and adverse events. Results We included 994 systematic reviews and meta‐analyses, including 32 that were review protocols, highlighting the distribution of psychotherapy, pharmacotherapy, and complementary and alternative treatments. However, the evidence and gap map (EGM) revealed significant gaps in evidence for specific interventions, populations, outcomes, and regions. While psychotherapy, pharmacotherapy, and complementary and alternative treatments dominate the landscape, the review highlighted a lack of research on interventions for specific types of depression, such as depression in people with bipolar disorder and treatment‐resistant depression. It was a similar situation for underserved populations, including young and middle‐aged adults, males, sexual minority individuals, and people with disabilities. The map also suggested the need for more research on the potential risks and side effects associated with both pharmacological and nonpharmacological treatments. Conclusions The contribution of this EGM was to present the available evidence on psychotherapy, pharmacotherapy, and complementary and alternative treatments for depression in adults, making available an evidence base that could inform future policy decisions and practice. It also identified evidence gaps in interventions, outcomes, population, regions, and evidence confidence. The need for further research on tailored treatments for specific populations was highlighted.

Natural Medications in Psychiatry

Chapter

Jan 2025

Natural Medications in Psychiatry

Chapter

Jan 2025

Application of proton magnetic resonance spectroscopy in metabolic alterations of prefrontal white and gray matter in depression adolescents

Article

Full-text available

Nov 2024

BACKGROUND Cases of depression among adolescents are gradually increasing. The study of the physiological basis of cognitive function from a biochemical perspective has therefore been garnering increasing attention. Depression has been hypothesized to be associated with the brain biochemical metabolism of the anterior cingulate gyrus, frontal lobe white matter, and the thalamus. AIM To explore the application of proton magnetic resonance spectroscopy (1H-MRS) in the metabolic alterations in the prefrontal white matter (PWM) and gray matter (GM) in adolescents with depression. METHODS 1H-MRS was performed for semi-quantitative analysis of the biochemical metabolites N-acetylaspartate (NAA), choline (Cho) complexes, creatine (Cr), and myo-inositol (mI) in bilateral PWM, anterior cingulate GM, and thalami of 31 adolescent patients with depression (research group) and 35 healthy adolescents (control group), and the NAA/Cr, Cho/Cr, and mI/Cr ratios were calculated. Meanwhile, Hamilton Depression Scale (HAMD) and Wechsler Memory Scale were used to assess the degree of depression and memory function in all adolescents. The correlation of brain metabolite levels with scale scores was also analyzed. RESULTS The research group had markedly higher HAMD-24 scores and lower memory quotient (MQ) compared with the control group (P < 0.05). Adolescents with depression were found to have lower bilateral PWM NAA/Cr and Cho/Cr ratios compared with healthy adolescents (P < 0.05). The mI/Cr ratios were found to be similar in both groups (P > 0.05). The bilateral anterior cingulate GM NAA/Cr, Cho/Cr, and mI/Cr also did not demonstrate marked differences (P > 0.05). No statistical inter-group difference was determined in NAA/Cr of the bilateral thalami (P > 0.05), while bilateral thalamic Cho/Cr and mI/Cr were reduced in teenagers with depression compared with healthy adolescents (P < 0.05). A significant negative correlation was observed between the HAMD-24 scores in adolescents with depression with bilateral PWM NAA/Cr and Cho/Cr and were inversely linked to bilateral thalamic Cho/Cr and mI/Cr (P < 0.05). In adolescents with depressions, MQ positively correlated with right PWH NAA/Cr, left PWH Cho/Cr, and bilateral thalamic Cho/Cr and mI/Cr. CONCLUSION PWM and thalamic metabolic abnormalities might influence teen depression, and the reduction in bilateral PWM NAA/Cr and Cho/Cr could be related to the neuropathology of adolescents with depression suffering from memory impairment. There exists a possibility of dysfunction of nerve cell membrane phospholipids in the thalami of adolescent patients with depression.

Integrative and Complementary Medicine in Psychiatry

Chapter

Sep 2024

Nutraceuticals, Dietary, and Herbal Supplements

Chapter

Jun 2024

Talia Puzantian

The use of over-the-counter supplements and nutraceuticals by aging adults over age 60 in the United States is common, with a 67% increase over 10 years (Mishra S, Dietary supplement use among adults: United States, 2017–2018. NCHS Data Brief, no 399. Hyattsville: National Center for Health Statistics, 2021). Over half of USA adults use at least one dietary supplement and use grows in advancing age, with an estimated 74.3% of those 60 and older taking dietary supplements (Mishra S, Dietary supplement use among adults: United States, 2017–2018. NCHS Data Brief, no 399. Hyattsville: National Center for Health Statistics, 2021). The number of supplements used also is greater with age, with a quarter of older adults taking four or more supplements. The most frequently used are multivitamin-mineral supplements, vitamin D, omega-3 fatty acids, calcium, and vitamin B12. Due to the paucity of evidence, clinicians may be unprepared to answer questions or make recommendations about these products. This chapter offers an overview of what is known regarding the efficacy and safety of various common supplements which have purported benefits for psychiatric symptoms and syndromes in aging adults. Improving and maintaining overall health are the most commonly reported reasons for taking supplements (Bailey RL, JAMA Intern Med 173:355–361, 2013). As people age, they tend to burn fewer calories, be less physically active, gradually lose lean muscle mass, need fewer calories, and experience decreased appetite. Therefore, aging adults may need more nutrients via supplementation to maintain proper health. Aging adults also report specific motivations for using supplements such as heart, bone/joint, or eye health (Bailey RL, JAMA Intern Med 173:355–361, 2013). This broadens the range of products typically used by the geriatric population to include not only dietary supplements but also medicinal herbs (sometimes referred to as phytoceuticals or phytochemicals) and other “natural products.” See Table 18.1.

Maternal Mood, Anxiety and Mental Health Functioning After Combined Myo-inositol, Probiotics, Micronutrient Supplementation from Preconception: findings from the NiPPeR RCT

Article

Feb 2024
PSYCHIAT RES

Observational studies have reported associations between nutrition during pregnancy and mental wellbeing. As secondary outcomes, the NiPPeR double-blind randomized trial in women planning conception investigated whether a myo-inositol, probiotics and enriched micronutrients formulation (intervention) taken preconception and throughout pregnancy could improve mental wellbeing during pregnancy and post-delivery, compared with a standard micronutrient supplement (control). Mood and anxiety symptoms were ascertained (Edinburgh Postnatal Depression Scale (EPDS), State-Trait Anxiety Inventory (STAI-state)) at preconception (baseline), 7, 28 and 34 weeks gestation, 3-weeks and 6-months post-delivery. EPDS>=13 was categorised as low mood; STAI-state>=45 as high anxiety. Change in mental health functioning was assessed as difference between preconception baseline and 6-month post-delivery 12-item Short-Form Health Survey (SF-12v2) mental component scores. Adjusting for site, ethnicity and baseline scores, there were no robust differences in EPDS and STAI-state scores between intervention and control groups across pregnancy (n = 630) and post-delivery (n = 532). Compared to controls, intervention group women averaged a 1.21 (95 %CI 0.04,2.39) higher change in SF-12v2 mental component score from preconception to 6-months post-delivery. Taking a myo-inositol, micronutrient and probiotic supplement during preconception/pregnancy had no effect on mood and anxiety, but there was evidence of a modest improvement in mental health functioning from preconception to 6-months post-delivery.

Identification of the Shared Gene Signatures and Molecular Mechanisms Between Polycystic Ovarian Syndrome and Major Depressive Disorder: Evidence From Transcriptome Data

Preprint

Full-text available

Dec 2023

Background: Polycystic Ovarian Syndrome (PCOS) is the most common metabolic and endocrine disorder in reproductive-age women, while Major Depressive Disorder (MDD) is a relatively common psychiatric condition. Previous studies have suggested a potential link between PCOS and MDD, but the underlying pathophysiological mechanisms remain unclear. This study aims to identify differential expression genes (DEGs) between PCOS and MDD using bioinformatics methods, explore the associated molecular mechanisms, elucidate the TF-mRNA-miRNA regulatory network involved, predict potential drug molecules, and validate them through molecular docking. Methods: Microarray datasets GSE34526 and GSE125664 were downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) of PCOS and MDD were analyzed using the GEO2R online tool to obtain shared DEGs to both. Next, the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis for the shared DEGs were performed. Then, protein-protein interaction (PPI) network were constructed and the hub genes were identified using the STRING database and Cytoscape software. Next, NetworkAnalyst was used to construct network between target transcription factors (TFs), microRNAs (miRNAs), and hub genes. Finally, the DSigDB database was used to search for potential drug molecules for the treatment of PCOS combined with MDD, followed by molecular docking using the AutoDock Tools and visualization of the results using PyMol 2.4.0. Results: In the above two datasets, 158 shared DEGs were identified. GO and KEGG enrichment analyses showed that these shared DEGs were mainly enriched in pathways related to neural signaling, energy metabolism, and chronic inflammation with immune dysregulation. In addition, genes with greater than 2-fold median interaction number were further screened by Cytoscape's plugin, cytoNCA, and finally 6 hub genes were selected from the PPI network, ncluding GRIN1, CNR1, DNM1, SYNJ1, PLA2G4A and EPHB2. Then, through the construction of the TF-mRNA-miRNA regulatory network, it was concluded that hsa-miR-27a might be a strongly associated miRNA with the pathogenesis of PCOS and MDD, while TFAP2A might be a strongly associated TF. Finally, orlistat, docosahexaenoic acid (DHA), capsaicin, and myo-inositol were considered as potential drug molecules for the treatment of PCOS combined with MDD using the DSigDB database and related study finding, and then molecular docking was performed using AutoDock Tools. The drug-molecule combination with the lowest binding energy was visualized using PyMol software and it found to be well docked. Conclusions: In summary, we constructed a TF-mRNA-miRNA regulatory network for the first time to characterize the interactions among potential TFs, miRNAs, and hub genes associated with PCOS and MDD, and concluded that aberrant neuronal signaling, disturbed energy metabolism, and immune dysregulation with inflammatory response may be the common pathogenesis of PCOS and MDD. In addition, we identified potential drug molecules for the treatment of PCOS and MDD and performed molecular docking validation. This provides new insights to identify potential associations, potential biomarkers and therapeutic agents for PCOS and MDD.

Marital Satisfaction in Postpartum Women: The Role of Personality, Body Image Satisfaction, Anxiety, and Sexual Function

Article

Nov 2023
Curr Wom Health Rev

Background The postpartum period is considered a vulnerable and stressful period for many women due to various hormonal, physical, and psychosocial changes, such as adapting to parental rules, changes in body and self-image, loss of autonomy, breastfeeding, and taking care of the baby Objective This study aimed to test a conceptual model considering the interrelated role of anxiety, body image satisfaction, sexual function, type of personality, income, and education on women’s marital satisfaction. Also it also aimed to test the mediating role of sexual function and anxiety. Methods In this cross-sectional study, 447 lactating women were recruited from January to April 2019. Women answered some questionnaires including a socio-demographic checklist, female sexual function index (FSFI), Body Self-Relation Questionnaire (BSRQ), the Enrich Marital Satisfaction, and the NEO Personality Inventory (NEO PI-R). Data were analyzed using the descriptive test, and Path analysis was done with LISREL software. Results Results show that sexual function (β= 0.44), anxiety (β= -0.26), and educational level (β= 0.47) are the main predictors of marital satisfaction (dependent variable). Sexual function and anxiety were two main mediators; variables, such as anxiety (β= -0.35), body image satisfaction (β= 0.19), and extraversion personality (β= 0.19) (independent variables), with an effect through sexual function, can impress marital satisfaction indirectly. Conclusion Identifying relationships between anxiety, educational level, sexual function, anxiety, body image, and personality with the quality of life of postpartum women highlights the importance of designing interventions to improve marital satisfaction. Given these relationships, it is recommended that health professionals educate women about body changes during postpartum and find ways to improve mothers' marital satisfaction.

PROTOCOL: Non‐pharmacological interventions for older people with a diagnosis of depression: An evidence and gap map

Article

Full-text available

Sep 2023

This is the protocol for an evidence and gap map. The objectives are as follows: To map available randomized control trials, economic evaluations, and systematic reviews that assess the effectiveness and cost‐effectiveness of non‐pharmacological interventions for older people with a diagnosis of depression and identify any existing gaps in the evidence that can inform future research.

Integrative and Complementary Medicine in Psychiatry

Chapter

Jun 2023

PROTOCOL: Treatment for depressive disorder among adults: An evidence and gap map of systematic reviews

Article

Full-text available

Mar 2023

This is the protocol for a Campbell evidence and gap map. The objective of the map is to map available systematic reviews on the effectiveness of treatments for depressive disorders among adults. Specifically, this EGM includes studies on the effectiveness of treatments across a range of outcome domains.

A Randomized, Double-Blind, Controlled Clinical Trial of Omega-3 Fatty Acids and Inositol as Monotherapies and in Combination for the Treatment of Pediatric Bipolar Spectrum Disorder in Children Age 5-12

Article

Oct 2022

Objectives: The aim of this study was to assess the efficacy and tolerability of omega-3 fatty acids (FAs) and inositol alone and in combination for the treatment of pediatric bipolar (BP) spectrum disorder in young children. Methods: Participants were male and female children ages 5-12 meeting DSM-IV diagnostic criteria for a BP spectrum disorder and displaying mixed, manic, or hypomanic symptoms without psychotic features at the time of evaluation. Results: Participants concomitantly taking psychotropic medication were excluded from efficacy analyses. There were significant reductions in YMRS and HDRS mean scores in the inositol and combination treatment groups (all p < 0.05) and in CDRS mean scores in the combination treatment group (p < 0.001), with the largest changes seen in the combination group. Those receiving the combination treatment had the highest rates of antimanic and antidepressant response. The odds ratios for the combination group compared to the omega-3 FAs and inositol groups were clinically meaningful (ORs ≥2) for 50% improvement on the YMRS, normalization of the YMRS (score <12) (vs. inositol group only), 50% improvement on the HDRS, 50% improvement on CDRS (vs. omega-3 FAs group only), and CGI-I Mania, CGI-I MDD, and CGI-I Anxiety scores <2. Conclusion: The antimanic and antidepressant effects of the combination treatment of omega-3 FAs and inositol were consistently superior to either treatment used alone. This combination may offer a safe and effective alternative or augmenting treatment for youth with BP spectrum disorder, but more work is needed to confirm the statistical significance of this finding.

Regional metabolic heterogeneity in anterior cingulate cortex in major depressive disorder: A multi-voxel 1H magnetic resonance spectroscopy study

Article

Sep 2022
J AFFECT DISORDERS

Background Previous studies have shown major depressive disorder (MDD) is associated with altered neuro-metabolites in the anterior cingulate cortex (ACC). However, the regional metabolic heterogeneity in the ACC in individuals with MDD remains unclear. Methods We recruited 59 first-episode, treatment-naive young adults with MDD and 50 healthy controls who underwent multi-voxel ¹H-MRS scanning at 3 T (Tesla) with voxels placed in the ACC, which was divided into two subregions, pregenual ACC (pACC) and anterior midcingulate cortex (aMCC). Between and within-subjects metabolite concentration variations were analyzed with SPSS. Results Compared with control subjects, patients with MDD exhibited higher glutamate (Glu) and glutamine (Gln) levels in the pACC and higher myo-inositol (MI) level in the aMCC. We observed higher Glu and Gln levels and lower N-acetyl-aspartate (NAA) level in the pACC than those in the aMCC in both MDD and healthy control (HC) groups. More importantly, the metabolite concentration gradients of Glu, Gln and NAA were more pronounced in MDD patients relative to HCs. In the MDD group, the MI level in the aMCC positively correlated with the age of onset. Limitations The use of the relative concentration of metabolites constitutes a key study limitation. Conclusions We observed inconsistent alterations and distribution of neuro-metabolites concentration in the pACC and aMCC, revealing regional metabolic heterogeneity of ACC in first-episode, treatment-naive young individuals with MDD. These results provided new evidence for abnormal neuro-metabolites of ACC in the pathophysiology of MDD and suggested that pACC and aMCC might play different roles in MDD.

Clinician guidelines for the treatment of psychiatric disorders with nutraceuticals and phytoceuticals: The World Federation of Societies of Biological Psychiatry (WFSBP) and Canadian Network for Mood and Anxiety Treatments (CANMAT) Taskforce

Article

Full-text available

Mar 2022
WORLD J BIOL PSYCHIA

Objectives: The therapeutic use of nutrient-based 'nutraceuticals' and plant-based 'phytoceuticals' for the treatment of mental disorders is common; however, despite recent research progress, there have not been any updated global clinical guidelines since 2015. To address this, the World Federation of Societies of Biological Psychiatry (WFSBP) and the Canadian Network for Mood and Anxiety Disorders (CANMAT) convened an international taskforce involving 31 leading academics and clinicians from 15 countries, between 2019 and 2021. These guidelines are aimed at providing a definitive evidence-informed approach to assist clinicians in making decisions around the use of such agents for major psychiatric disorders. We also provide detail on safety and tolerability, and clinical advice regarding prescription (e.g. indications, dosage), in addition to consideration for use in specialised populations. Methods: The methodology was based on the WFSBP guidelines development process. Evidence was assessed based on the WFSBP grading of evidence (and was modified to focus on Grade A level evidence - meta-analysis or two or more RCTs - due to the breadth of data available across all nutraceuticals and phytoceuticals across major psychiatric disorders). The taskforce assessed both the 'level of evidence' (LoE) (i.e. meta-analyses or RCTs) and the assessment of the direction of the evidence, to determine whether the intervention was 'Recommended' (+++), 'Provisionally Recommended' (++), 'Weakly Recommended' (+), 'Not Currently Recommended' (+/-), or 'Not Recommended' (-) for a particular condition. Due to the number of clinical trials now available in the field, we firstly examined the data from our two meta-reviews of meta-analyses (nutraceuticals conducted in 2019, and phytoceuticals in 2020). We then performed a search of additional relevant RCTs and reported on both these data as the primary drivers supporting our clinical recommendations. Lower levels of evidence, including isolated RCTs, open label studies, case studies, preclinical research, and interventions with only traditional or anecdotal use, were not assessed. Results: Amongst nutraceuticals with Grade A evidence, positive directionality and varying levels of support (recommended, provisionally recommended, or weakly recommended) was found for adjunctive omega-3 fatty acids (+++), vitamin D (+), adjunctive probiotics (++), adjunctive zinc (++), methylfolate (+), and adjunctive s-adenosyl methionine (SAMe) (+) in the treatment of unipolar depression. Monotherapy omega-3 (+/-), folic acid (-), vitamin C (-), tryptophan (+/-), creatine (+/-), inositol (-), magnesium (-), and n-acetyl cysteine (NAC) (+/-) and SAMe (+/-) were not supported for this use. In bipolar disorder, omega-3 had weak support for bipolar depression (+), while NAC was not currently recommended (+/-). NAC was weakly recommended (+) in the treatment of OCD-related disorders; however, no other nutraceutical had sufficient evidence in any anxiety-related disorder. Vitamin D (+), NAC (++), methylfolate (++) were recommended to varying degrees in the treatment of the negative symptoms in schizophrenia, while omega-3 fatty acids were not, although evidence suggests a role for prevention of transition to psychosis in high-risk youth, with potential pre-existing fatty acid deficiency. Micronutrients (+) and vitamin D (+) were weakly supported in the treatment of ADHD, while omega-3 (+/-) and omega-9 fatty acids (-), acetyl L carnitine (-), and zinc (+/-) were not supported. Phytoceuticals with supporting Grade A evidence and positive directionality included St John's wort (+++), saffron (++), curcumin (++), and lavender (+) in the treatment of unipolar depression, while rhodiola use was not supported for use in mood disorders. Ashwagandha (++), galphimia (+), and lavender (++) were modestly supported in the treatment of anxiety disorders, while kava (-) and chamomile (+/-) were not recommended for generalised anxiety disorder. Ginkgo was weakly supported in the adjunctive treatment of negative symptoms of schizophrenia (+), but not supported in the treatment of ADHD (+/-). With respect to safety and tolerability, all interventions were deemed to have varying acceptable levels of safety and tolerability for low-risk over-the-counter use in most circumstances. Quality and standardisation of phytoceuticals was also raised by the taskforce as a key limiting issue for firmer confidence in these agents. Finally, the taskforce noted that such use of nutraceuticals or phytoceuticals be primarily recommended (where supportive evidence exists) adjunctively within a standard medical/health professional care model, especially in cases of more severe mental illness. Some meta-analyses reviewed contained data from heterogenous studies involving poor methodology. Isolated RCTs and other data such as open label or case series were not included, and it is recognised that an absence of data does not imply lack of efficacy. Conclusions: Based on the current data and clinician input, a range of nutraceuticals and phytoceuticals were given either a supportive recommendation or a provisional recommendation across a range of various psychiatric disorders. However several had only a weak endorsement for potential use; for a few it was not possible to reach a clear recommendation direction, largely due to mixed study findings; while some other agents showed no obvious therapeutic benefit and were clearly not recommended for use. It is the intention of these guidelines to inform psychiatric/medical, and health professional practice globally.

Current Research on Complementary and Alternative Medicine (CAM) in the Treatment of Major Depressive Disorder: An Evidence-Based Review

Chapter

Apr 2021
ADV EXP MED BIOL

Complementary and alternative medicine (CAM) encompasses a wide range of different non-mainstream therapies that have been increasingly used for treatment or adjunctive treatment of various ailments with mood disorders and “depressive difficulties” being two of the commonly CAM (self-)medicated conditions. We focus specifically on clinically diagnosed (in line with the standard criteria) depressive disorders, primarily major depressive disorder (MDD), and overview evidence of efficacy/safety of a range of CAM modalities addressing exclusively randomized controlled trials (RCTs) and systematic reviews/meta-analyses of RCTs. The list of addressed CAM interventions is not exhaustive: due to space limitation, addressed are interventions with at least a few conducted RCTs in the specific clinical conditions. We try to provide numerical and meaningful data as much as it is possible and to (a) indicate situations in which the reported data/estimates might have been “too enthusiastic” and (b) warn about heterogeneity of results that, together with other possible limitations (various biases and imprecision), results in uncertainty about the effects.

Inositols in reproductive medicine

Article

Full-text available

Dec 2020

У статті поданий огляд літературних даних щодо ролі інозитолу та його похідних в організмі людини, результати використання міо-інозитолу (МІ) при гінекологічних захворюваннях, лікуванні жіночого та чоловічого безпліддя, у тому числі в циклах допоміжних репродуктивних технологій, в профілактиці гестаційних і перинатальних ускладнень. Показано, що нездатність адекватно синтезувати або метаболізувати інозитол може сприяти порушенням передачі внутрішньоклітинних сигналів, порушенню активності сигнальних каскадів інсуліну, розвитку резистентності до інсуліну та гіперінсулінемії, що викликає аномальний стероїдогенез у гонадах і метаболічні порушення. Висвітлена концепція «парадоксу D-хіро-інозитолу», відповідно до якої для жінок із синдромом полікістозних яєчників характерна посилена епімеризація МІ в D-хіро-інозитол, виснаження запасів МІ і, як наслідок, низька якість ооцитів. Доведено, що призначення вагітним біологічно активних добавок з МІ та фолієвою кислотою знижує ймовірність загрози переривання вагітності, прееклампсії, плацентарної дисфункції, гестаційного цукрового діабету, діабетичної фетопатії, вад розвитку, а також оксидативний стрес у плода. Накопичений досвід застосування міо-інозитолу в андрології: він відіграє вирішальну роль в осморегуляції сім’яної рідини і, як наслідок, у збільшенні прогресивної рухливості і швидкості сперматозоїдів, підвищенні мітохондріального потенціалу сперматозоїдів, покращує лібідо та потенцію, сприяє підвищенню рівня ендогенного тестостерону, нормалізує гормональний фон чоловіків. Інозитоли є синергістами фолатів та інших вітамінів групи В і значуще потенціюють їхній вплив на організм людини, що є підґрунтям переваги використання в клініці жіночої та чоловічої репродукції комбінованих біологічних добавок, таких як Міофолік® та Міофолік® MEN. Гармонійне використання всіх можливих резервів мікронутрієнтної підтримки преконцепційного та гестаційного періоду із застосуванням біологічно активних добавок МІ в комбінації з фолієвою кислотою та вітаміном В12 є перспективним профілактичним і лікувальним методом у підтримці функціонування репродуктивної системи, розвитку ембріона, нейропротекції мозку плода, забезпеченні активності сигнальних каскадів інсуліну.

Multitarget Activities of Inositol and Inositol Hexakisphosphate

Chapter

Apr 2020

Ivana Vucenik

Multiple health beneficial effects have been shown for inositol hexakisphosphate (IP6) and its parent compound myo-inositol (Ins) in animal and human studies. However, the most striking is their consistent and reproducible anticancer effect, actively investigated and demonstrated in various experimental models during the last decades. Key molecular targets for cancer are PI3K/Akt, MAPK, PKC, AP-1 and NF-κB. Reduced burden of chemotherapy side-effects in cancer patients receiving IP6 alone or in combination with Ins, have been reported. However, modulation of both insulin resistance and cancer by Ins and IP6 have been indicated, and therefore there is a need for specific, randomized clinical trials and further mechanistic studies.

Revisiting the Concept of Human Disease: Rethinking the Causality Concept in Pathogenesis for Establishing a Different Pharmacological Strategy

Chapter

Apr 2020

Current network-based models, their heuristic and epistemological value notwithstanding, only partially explain the unfathomable complexity behind the outbreak of a disease, as they are habitually centered on an integrated representation of the cell biochemical and genetic pathways, and, as such, they discard the contribution of non-genetic factors and microenvironmental constraints. Thereby, since the eighties, the agenda of pharmacology discovery was then dictated by aiming at discovering “relevant” molecules (along with their classical rules of interaction), abstracting from the true, physiological response of cells, tissues and organism. In this perspective, genes assume the fundamental causal role while cells simply act as causal proxies, dispensable because they represent an irrelevant intermediate level between the molecular input and the organismal output. Such framework, both theoretically and methodologically, is no longer tenable. We propose herein a comprehensive model able in capturing the complexity on which the disease relies, thus recognizing a different spatially (multi-level) and timely distributed target array. Moreover, given that a disease is properly a dynamic process and not a steady state, treatments should also be diversified according to the timing of the disease process. This approach can help in detecting pre-disease state or critical transition points from which the illness might access different attractors, leading ultimately to different outcomes. We should thus design systems-oriented drugs that tackle both the multifactorial pathogenic determinants of the disease as well as the intrinsic robustness of the living organism, by promoting a polyvalent-based approach, i.e. the use of multiple drugs or drugs affecting several targets localized at different levels. Additionally, above and beyond classical pharmacodynamics, unconventional mechanisms of action urge to be investigated and integrated within network modelling. Overall, this implies that we should shift from targets to processes, to “redraw” the disease-related landscape, favoring the system displacement from pre-clinical state or true disease-states towards healing pathways.

Current Research on Complementary and Alternative Medicine (CAM) in the Treatment of Anxiety Disorders: An Evidence-Based Review

Chapter

Jan 2020
ADV EXP MED BIOL

Complementary and alternative medicine (CAM) encompasses a wide range of different nonmainstream therapies that have been increasingly used for treatment or adjunctive treatment of various ailments with anxiety/anxiety disorders being one of the commonly CAM (self)-medicated conditions. Thousands of published papers refer to use of CAM in various psychiatric disorders or in healthy or medically ill patients with mood or anxiety difficulties. In this chapter we focus specifically on clinically diagnosed (in line with the standard criteria) anxiety disorders and overview evidence of efficacy/safety of a range of CAM modalities: biologically based therapies (typically herbal preparations and less so nutraceuticals); manipulative and body-based therapies (acupuncture, aerobic exercise, massage, therapeutic touch, repetitive transcranial magnetic stimulation, balneotherapy, and others); mind-body therapies (yoga, Morita therapy, Tai Chi, reiki, Chinese cognitive therapy, religious and spiritual interventions, relaxation, mediation, and mindfulness-based interventions); and alternative medical systems (Ayurveda, homeopathy). We focus exclusively on randomized controlled trials and attempt to evaluate the existing body of evidence in the same manner that is applied to mainstream treatments.

Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement

Article

Full-text available

Jan 2014

Systematic reviews should build on a protocol that describes the rationale, hypothesis, and planned methods of the review; few reviews report whether a protocol exists. Detailed, well-described protocols can facilitate the understanding and appraisal of the review methods, as well as the detection of modifications to methods and selective reporting in completed reviews. We describe the development of a reporting guideline, the Preferred Reporting Items for Systematic reviews and Meta-Analyses for Protocols 2015 (PRISMA-P 2015). PRISMA-P consists of a 17-item checklist intended to facilitate the preparation and reporting of a robust protocol for the systematic review. Funders and those commissioning reviews might consider mandating the use of the checklist to facilitate the submission of relevant protocol information in funding applications. Similarly, peer reviewers and editors can use the guidance to gauge the completeness and transparency of a systematic review protocol submitted for publication in a journal or other medium.

The neurobiology of depression - Revisiting the serotonin hypothesis. I. Cellular and molecular mechanisms

Article

Full-text available

Jan 2011

The serotonin (5-HT) hypothesis of depression dates from the 1960s. It originally postulated that a deficit in brain serotonin, corrected by antidepressant drugs, was the origin of the illness. Nowadays, it is generally accepted that recurring mood disorders are brain diseases resulting from the combination , to various degrees, of genetic and other biological as well as environmental factors, evolving through the lifespan. All areas of neuroscience, from genes to behaviour, molecules to mind, and experimental to clinical, are actively engaged in attempts at elucidating the pathophysiology of depression and the mechanisms underlying the efficacy of antidepressant treatments. This first of two special issues of Philosophical Transactions B seeks to provide an overview of current developments in the field, with an emphasis on cellular and molecular mechanisms, and how their unravelling opens new perspectives for future research.

.Reduced frontal cortex levels in postmortem brain of suicide victims and patients with bipolar disorder

Article

Full-text available

Jan 1998
AM J PSYCHIAT

OBJECTIVE: This study aimed to evaluate aspects of second messenger function in the brain of suicide victims and patients with bipolar disorder. METHOD: Inositol and its synthetic enzyme, inositol monophosphatase, were measured in postmortem brain samples of 10 suicide victims, eight patients with bipolar affective disorder, and 10 normal comparison subjects. RESULTS: The frontal cortex inositol levels of the suicide victims and the patients with bipolar disorder were significantly less than those of the normal comparison group. No differences in cerebellum or occipital cortex inositol levels were found among the three groups. The groups also showed no differences in inositol monophosphatase activity in any brain area. CONCLUSIONS: These results could suggest a deficiency of second messenger precursor in patients with bipolar disorder and suicide victims.

.Double-blind, controlled trial of inositol treatment of depression

Article

Full-text available

Jun 1995
AM J PSYCHIAT

OBJECTIVE: CSF levels of inositol have been reported to be lower than normal in depressed subjects. The authors administered inositol to depressed patients in a double-blind, controlled trial. METHOD: Under double-blind conditions, 12 g/day of inositol (N = 13) or placebo (N = 15) was administered to depressed patients for 4 weeks. RESULTS: The overall improvement in scores on the Hamilton Depression Rating Scale was significantly greater for inositol than for placebo at week 4. No changes were noted in hematology or in kidney or liver function. CONCLUSIONS: This may be the first use of the precursor strategy for a second messenger rather than a neurotransmitter in treating depression. Although inositol had a significant antidepressant effect in this study, replication is crucial.

The neurobiology of depression--revisiting the serotonin hypothesis. II. Genetic, epigenetic and clinical studies

Article

Full-text available

Apr 2013
PHILOS T R SOC B

The serotonin system originates from a small number of neurons (a few hundred thousand of the 100 billion in man) located in the midbrain raphe nuclei, that project widely throughout the central nervous system to influence a large array of inter-related biological functions, not least of which are circuits involved in mood and emotion. The serotonin hypothesis of depression has postulated that a reduction in serotonin leads to increased predisposition to depression. Indeed, it has become evident from therapeutic strategies that affect serotonin activity, that alterations in serotonin may not only predispose to depression, but also to aggressive behaviour, impulsivity, obsessive-compulsive behaviour and suicide. Many potential mechanisms known to alter the genes that regulate the serotonin system, including developmental epigenetic modifications, are presented, as additional evidence implicating the serotonin system. This second issue of two special issues of Philosophical Transactions B presents a series of reviews, perspectives and new findings that argue that the serotonin hypothesis remains an important idea that continues to guide research into the aetiology and treatment of depression.

.Inositol versus placebo aumentation of serotonin reuptake inhibitor in the treatment of obsessive-compulsive disorder: A double-blind cross-over study

Article

Full-text available

Aug 1999
INT J NEUROPSYCHOPH

Current serotonin reuptake inhibitor (SRI) treatments for obsessive–compulsive disorder (OCD) provide only partial benefit. A previous study suggested that inositol alone is efficacious in OCD. Ten DSM-IV OCD patients completed a study of 18 g inositol or placebo for 6 wk each in addition to ongoing SRI treatment in a double-blind randomized cross-over design. Weekly assessments included the Yale–Brown Obsessive–Compulsive Scale (YBOCS) and Hamilton Depression and Anxiety scales. No significant difference was found between the two treatment phases.

Introduction: The neurobiology of depression—revisiting the serotonin hypothesis. I. Cellular and molecular mechanisms

Article

Full-text available

Sep 2012
PHILOS T R SOC B

The serotonin (5-HT) hypothesis of depression dates from the 1960s. It originally postulated that a deficit in brain serotonin, corrected by antidepressant drugs, was the origin of the illness. Nowadays, it is generally accepted that recurring mood disorders are brain diseases resulting from the combination, to various degrees, of genetic and other biological as well as environmental factors, evolving through the lifespan. All areas of neuroscience, from genes to behaviour, molecules to mind, and experimental to clinical, are actively engaged in attempts at elucidating the pathophysiology of depression and the mechanisms underlying the efficacy of antidepressant treatments. This first of two special issues of Philosophical Transactions B seeks to provide an overview of current developments in the field, with an emphasis on cellular and molecular mechanisms, and how their unravelling opens new perspectives for future research.

Premenstrual Dysphoric Disorder: Evidence for a New Category for DSM-5

Article

Full-text available

May 2012
AM J PSYCHIAT

Premenstrual dysphoric disorder, which affects 2%–5% of premenopausal women, was included in Appendix B of DSMIV, "Criterion Sets and Axes Provided for Further Study." Since then, aided by the inclusion of specific and rigorous criteria in DSM-IV, there has been an explosion of research on the epidemiology, phenomenology, pathogenesis, and treatment of the disorder. In 2009, the Mood Disorders Work Group for DSM-5 convened a group of experts to examine the literature on premenstrual dysphoric disorder and provide recommendations regarding the appropriate criteria and placement for the disorder in DSM-5. Based on thorough review and lengthy discussion, the work group proposed that the information on the diagnosis, treatment, and validation of the disorder has matured sufficiently for it to qualify as a full category in DSM-5. A move to the position of category, rather than a criterion set in need of further study, will provide greater legitimacy for the disorder and encourage the growth of evidence-based research, ultimately leading to new treatments.

Myo-inositol in the treatment of premenstrual dysphoric disorder

Article

Full-text available

Oct 2011
HUM PSYCHOPHARM CLIN

Premenstrual dysphoric disorder (PMDD) is a mood disorder disrupting social and/or occupational life of affected women. Premenstrual dysphoric disorder etiology is unknown, although a pivotal role is played by the serotoninergic system. Indeed, one of the most effective treatments is selective serotonin reuptake inhibitors. Several studies have proposed a selective serotonin reuptake inhibitor-like role for myo-inositol, likely due to the fact that myo-inositol is the second messenger of serotonin. In the present study, we aimed to investigate the effect of myo-inositol in the treatment of PMDD. We used a two-phase clinical trial approach (phase I: placebo washout; phase II: comparisons between treatment and placebo) and treated PMMD patients with two different myo-inositol formulations: powder or soft gel capsules. We decided to test these two formulations because according to the manufacturer, 0.6 g of myo-inositol in soft gel capsule has a pharmacokinetic equivalent to 2 g of myo-inositol in powder. Our results showed a significant improvement of three different scales: a reduction in the Daily Symptoms Records scale and an improvement of the Hamilton Depression Rating and Clinical Global Impression-Severity of Illness scales. Results were similar for both formulations. In the present study, by using a new pharmaceutical formulation, we were able to clearly prove the efficacy of myo-inositol in PMDD.

Moher D, Liberati A, Tetzlaff J, Altman DG, Group PPreferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 6: e1000097

Article

Full-text available

Jul 2009

David Moher and colleagues introduce PRISMA, an update of the QUOROM guidelines for reporting systematic reviews and meta-analyses

.Inositol treatment for panic disorder: a double-blind placebo-controlled crossover trial

Article

Full-text available

Aug 1995

Because they found in an earlier study that inositol, an important intracellular second-messenger precursor, was effective against depression in open and double-blind trials, the authors studied its effectiveness against panic disorder. Twenty-one patients with panic disorder with or without agoraphobia completed a double-blind, placebo-controlled, 4-week, random-assignment crossover treatment trial of 12 g/day of inositol. The frequency and severity of panic attacks and the severity of agoraphobia declined significantly more after inositol than after placebo administration. Side effects were minimal. The authors conclude that inositol's efficacy, the absence of significant side effects, and the fact that inositol is a natural component of the human diet make it a potentially attractive therapeutic for panic disorder.

.Inositol treatment of obsessive-compulsive disorder

Article

Full-text available

Oct 1996

Earlier studies reported that inositol, a simple polyol second messenger precursor, was effective in controlled trials for patients with depression and panic. In this study its effectiveness in obsessive-compulsive disorder was investigated. Thirteen patients with obsessive-compulsive disorder completed a double-blind, controlled crossover trial of 18 g/day of inositol or placebo for 6 weeks each. The subjects had significantly lower scores on the Yale-Brown Obsessive Compulsive Scale when taking inositol than when taking placebo. The authors conclude that inositol is effective in depression, panic, and obsessive-compulsive disorder, a spectrum of disorders responsive to selective serotonin reuptake inhibitors.

Shimon H, Agam G, Belmaker RH, Hyde TM, Kleinman JE. Reduced frontal cortex inositol levels in postmortem brain of suicide victims and patients with bipolar disorder. Am J Psychiatry 154: 1148-1150

Article

Full-text available

Sep 1997

This study aimed to evaluate aspects of second messenger function in the brain of suicide victims and patients with bipolar disorder. Inositol and its synthetic enzyme, inositol monophosphatase, were measured in postmortem brain samples of 10 suicide victims, eight patients with bipolar affective disorder, and 10 normal comparison subjects. The frontal cortex inositol levels of the suicide victims and the patients with bipolar disorder were significantly less than those of the normal comparison group. No differences in cerebellum or occipital cortex inositol levels were found among the three groups. The groups also showed no differences in inositol monophosphatase activity in any brain area. These results could suggest a deficiency of second messenger precursor in patients with bipolar disorder and suicide victims.

.Inositol addition does not improve depression in SSRI treatment failures

Article

Full-text available

Feb 1999

Some antidepressants, such as Lithium, can augment the antidepressant effect of serotonin selective uptake inhibitors (SSRI) in patients who have failed to respond to SSRI. Inositol has demonstrated antidepressant effects but in a controlled double blind augmentation trial did not improve depression in SSRI treatment failures.

Measuring Inconsistency in Meta-Analyses

Article

Full-text available

Oct 2003
Br Med J

Cochrane Reviews have recently started including the quantity I 2 to help readers assess the consistency of the results of studies in meta-analyses. What does this new quantity mean, and why is assessment of heterogeneity so important to clinical practice? Systematic reviews and meta-analyses can provide convincing and reliable evidence relevant to many aspects of medicine and health care.1 Their value is especially clear when the results of the studies they include show clinically important effects of similar magnitude. However, the conclusions are less clear when the included studies have differing results. In an attempt to establish whether studies are consistent, reports of meta-analyses commonly present a statistical test of heterogeneity. The test seeks to determine whether there are genuine differences underlying the results of the studies (heterogeneity), or whether the variation in findings is compatible with chance alone (homogeneity). However, the test is susceptible to the number of trials included in the meta-analysis. We have developed a new quantity, I 2, which we believe gives a better measure of the consistency between trials in a meta-analysis. Assessment of the consistency of effects across studies is an essential part of meta-analysis. Unless we know how consistent the results of studies are, we cannot determine the generalisability of the findings of the meta-analysis. Indeed, several hierarchical systems for grading evidence state that the results of studies must be consistent or homogeneous to obtain the highest grading.2–4 Tests for heterogeneity are commonly used to decide on methods for combining studies and for concluding consistency or inconsistency of findings.5 6 But what does the test achieve in practice, and how should the resulting P values be interpreted? A test for heterogeneity examines the null hypothesis that all studies are evaluating the same effect. The usual test statistic …

Measuring inconsistency in meta-analysis

Article

Jan 2003

The Yale-Brown Obsessive Compulsive Scale

Article

Nov 1989
ARCH GEN PSYCHIAT

Wayne Goodman

• The Yale-Brown Obsessive Compulsive Scale was designed to remedy the problems of existing rating scales by providing a specific measure of the severity of symptoms of obsessivecompulsive disorder that is not influenced by the type of obsessions or compulsions present. The scale is a clinician-rated, 10-item scale, each item rated from 0 (no symptoms) to 4 (extreme symptoms) (total range, 0 to 40), with separate subtotals for severity of obsessions and compulsions. In a study involving four raters and 40 patients with obsessive-compulsive disorder at various stages of treatment, interrater reliability for the total Yale-Brown Scale score and each of the 10 individual items was excellent, with a high degree of internal consistency among all item scores demonstrated with Cronbach's α coefficient. Based on pretreatment assessment of 42 patients with obsessive-compulsive disorder, each item was frequently endorsed and measured across a range of severity. These findings suggest that the Yale-Brown Scale is a reliable instrument for measuring the severity of illness in patients with obsessive-compulsive disorder with a range of severity and types of obsessive-compulsive symptoms.

Myoinositol has no Beneficial Effect on Premenstrual Dysphoric Disorder

Article

Jul 2002

Inositol, a simple isomer of glucose, which serves as a precursor in the phosphatidyl-inositol (PI) second messenger cycle, was shown to be effective in double-blind, placebo-controlled studies of depression, panic and obsessive compulsive disorders as well as in bulimia. The following study was designed to investigate whether inositol has beneficial effects in another disorder shown to be responsive to SSRIs: premenstrual dysphoric disorder (PMDD). Eleven female patients with PMDD diagnosed according to DSM-IV participated in a cross-over, double-blind, placebo-controlled trial. The active drug was myo-inositol, 12 g daily, whereas placebo was d-glucose administered at the same dose. Each drug was given during the luteal phase only (14 days prior to menses). for each patient treatment alternated between these two drugs for six menstrual cycles. No beneficial effect was demonstrated for inositol over placebo.

Reduced myo-inositol levels in cerebrospinal fluid from patients with affective disorder.

Article

Feb 1978
BIOL PSYCHIAT

Amiram I Barkai

Cerebrospinal fluid (CSF) from 14 hospitalized patients with primary affective disorder was analyzed for myo-inositol, glucose, and fructose before and after administration of probenecid. Compared with values from 3 control Ss who were not psychiatrically ill, the mean concentration of myo-inositol but not of glucose or fructose appears to be significantly lower in the CSF of depressed patients. When patients were divided into 3 affective disorder subtypes, the levels of both inositol and glucose decreased in the order Unipolar > Bipolar I > Bipolar II, and a linear relationship was established between the concentration of myo-inositol and glucose in the CSF samples. It is suggested that the level of free myo-inositol is dependent in part on the level of glucose available as a precursor for its synthesis by the CNS, thus the reduction of myo-inositol might reflect a decreased synthesis of cerebral inositol in depressed patients. (22 ref) (PsycINFO Database Record (c) 2012 APA, all rights reserved)

Nutraceuticals in the treatment of Obsessive Compulsive Disorder (OCD): A review of mechanistic and clinical evidence

Article

Feb 2011

Obsessive-compulsive disorder (OCD) is a debilitating mental illness which has a significant impact on quality of life. First-line SSRI treatments for OCD typically are of limited benefit to only 40-60% of patients, and are associated with a range of adverse side effects. Current preclinical research investigating nutraceuticals (natural products) for OCD, reveals encouraging novel activity in modulating key pathways suggested to be involved in the pathogenesis of OCD (glutamatergic and serotonergic pathway dysregulation). Emerging clinical evidence also appears to tentatively support certain nutrients and plant-based interventions with known active constituents which modulate these pathways: N-acetlycysteine, myo-inositol, glycine, and milk thistle (Silybum marianum). The serotonin precursor tryptophan is unlikely to be of use in treating OCD while 5-HTP may possibly be a more effective precursor strategy. However, there is currently no clinical evidence to test the efficacy of either of these substances. Currently the balance of clinical evidence does not support the use of St. John's wort (Hypericum perforatum) in OCD. While clinical research in this area is in its infancy, further research into nutraceuticals is warranted in light of the promising preclinical data regarding their mechanisms of action and their favourable side effect profiles in comparison to current SSRI treatments. It is recommended that future clinical trials of nutraceutical treatments for OCD utilize randomized placebo-controlled study designs and considerably larger sample sizes in order to properly test for efficacy.

Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, Moher D, Becker BJ, Sipe TA, Thacker SB. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group

Article

Jan 2000

Preferred Reporting Items for Systematic Reviews and Meta-Analyses: the PRISMA Statement

Article

Sep 2009

Reduced myo-inositol levels in cerebrospinal fluid from patients with affective disorder

Article

Mar 1978
BIOL PSYCHIAT

Cerebrospinal fluid from hospitalized patients with primary affective disorder was analyzed for myo-inositol, glucose, and fructose before and after administration of probenecid. The sugars were assayed simultaneously as trimethyl-silylated derivatives by a gas chromatographic method, and the following mean concentrations were obtained: fructose, 22.6 μg/ml; glucose, 680 μg/ml; and myo-inositol, 16.7 μg/ml. Compared with values from three control subjects, the mean concentration of myo-inositol but not of glucose or fructose appears to be significantly lower in the cerebrospinal fluid of depressed patients. When patients were divided into three affective disorder subtypes, the levels of both inositol and glucose decreased in the order Unipolar >Bipolar I>Bipolar II, and a liner relationship was established between the concentrations of myoinositol and glucose in the cerebrospinal fluid samples. It is suggested that the level of free myo-inositol is dependent in part on the level of glucose available as a precursor for its synthesis by the central nervous system, thus the reduction of myo-inositol might reflect a decreased synthesis of cerebral inositol in depressed patients. Probenecid did not influence the concentrations of these sugars indicating both that the drug does not interfere with cerebral synthesis of myo-inositol and that the transport of the sugars between cerebrospinal fluid and blood is not sensitive to probenecid.

The Yale-Brown Obsessive Compulsive Scale. I. Development, use and reliability

Article

Dec 1989
ARCH GEN PSYCHIAT

The Yale-Brown Obsessive Compulsive Scale was designed to remedy the problems of existing rating scales by providing a specific measure of the severity of symptoms of obsessive-compulsive disorder that is not influenced by the type of obsessions or compulsions present. The scale is a clinician-rated, 10-item scale, each item rated from 0 (no symptoms) to 4 (extreme symptoms) (total range, 0 to 40), with separate subtotals for severity of obsessions and compulsions. In a study involving four raters and 40 patients with obsessive-compulsive disorder at various stages of treatment, interrater reliability for the total Yale-Brown Scale score and each of the 10 individual items was excellent, with a high degree of internal consistency among all item scores demonstrated with Cronbach's alpha coefficient. Based on pretreatment assessment of 42 patients with obsessive-compulsive disorder, each item was frequently endorsed and measured across a range of severity. These findings suggest that the Yale-Brown Scale is a reliable instrument for measuring the severity of illness in patients with obsessive-compulsive disorder with a range of severity and types of obsessive-compulsive symptoms.

Meta-Analysis in Clinical Trials

Article

Oct 1986
Contr Clin Trials

This paper examines eight published reviews each reporting results from several related trials. Each review pools the results from the relevant trials in order to evaluate the efficacy of a certain treatment for a specified medical condition. These reviews lack consistent assessment of homogeneity of treatment effect before pooling. We discuss a random effects approach to combining evidence from a series of experiments comparing two treatments. This approach incorporates the heterogeneity of effects in the analysis of the overall treatment efficacy. The model can be extended to include relevant covariates which would reduce the heterogeneity and allow for more specific therapeutic recommendations. We suggest a simple noniterative procedure for characterizing the distribution of treatment effects in a series of studies.

.Inositol treatment in psychiatry

Article

Feb 1995
Psychopharmacol Bull

Inositol, a naturally occurring isomer of glucose, is a key intermediate of the phosphatidyl-inositol (PI) cycle, a second-messenger system used by several noradrenergic, serotonergic and cholinergic receptors. The suggestion that lithium might treat mania via its reduction of inositol levels led to experiments showing that pharmacological doses of peripheral inositol reverse behavioral effects of lithium in animals and side effects of lithium in man. Cerebrospinal fluid (CSF) levels of inositol are low in depression. An open-label, add-on trial of inositol in depression suggested a beneficial effect. In a subsequent 1-month, parallel-groups, double-blind, placebo-controlled study of 28 patients, inositol was effective as sole therapy for depression (p = .043). Inositol was also effective for panic disorder in a double-blind, random-assignment, placebo-controlled crossover study of 21 patients, with 4 weeks in each phase (p = .02); the effect was comparable to that of imipramine in recent studies.

Inositol treatment of post‐traumatic stress disorder

Article

Jan 1996

Keywords:PTSD;inositol;placebo;double-blind;crossover

Mixed anxiety and depression: From theory to practice

Article

Feb 1997

The 10th International Classification of Disease (ICD-10) introduced the concept of mixed anxiety-depression to define patients presenting both anxiety and depressive symptoms of limited number and/or intensity, not sufficiently severe to fulfill criteria for a specific diagnosis of depressive or anxiety disorder. Epidemiologic surveys have shown that these patients may display significant levels of functional impairment, have unexplained somatic symptoms and a high use of nonpsychiatric medical care, have long-lasting symptoms, and are at risk for more severe psychiatric disorders. A DSM-IV field trial concluded that patients with affective-symptoms not meeting thresholds for DSM-III-R disorders were at least as common as patients with anxiety or mood disorders, and that their symptoms were associated with significant distress or impairment. Although some of these patients present residual symptoms from previous psychiatric episodes and may request treatment specific to these conditions, it is not known if those without a psychiatric history could benefit from pharmacologic or psychological treatments usually used in mild outpatient cases.

.Combination of inositol and serotonin reuptake inhibitors in the treatment of depression

Article

Mar 1999
BIOL PSYCHIAT

Inositol has been reported to be an effective treatment in depression, and we hypothesized that inositol addition might enhance or speed up response to serotonin selective reuptake inhibitors (SSRI). Twenty-seven depressed patients completed a double-blind controlled 4-week trial of SSRI plus placebo or SSRI plus inositol. Hamilton Depression Rating Scale was used as an assessment tool at baseline, and 1, 2, 3, and 4 weeks. No significant difference was found between the two treatment groups. Previous studies combining different effective antidepressant therapies similarly found no evidence for additive effects [e.g., monoamine oxidase inhibitors (MAOI) plus tricyclic antidepressants (TCA), TCA plus lithium]. By contrast, augmentation by lithium or MAOI after a failed course of antidepressant treatment is effective and should be studied with inositol.

Inositol as an add‐on treatment for bipolar depression

Article

Apr 2000

Inositol is a constituent of the intracellular phosphatidyl inositol (PI) second messenger system, which is linked to various neurotransmitter receptors. Inositol crosses the blood-brain barrier in pharmacological doses, and has shown efficacy in a small double-blind study of unipolar depression. This pilot study evaluated its potential efficacy and safety in bipolar depression. Twenty-four consenting adult men and women with DSM-IV bipolar depression (bipolar I = 21; bipolar II = 3) were randomly assigned to receive either 12 g of inositol or D-glucose as placebo for 6 weeks. Efficacy and safety ratings were done weekly. Thymoleptic medications (lithium, valproate, carbamazepine) in stable doses and at therapeutic levels at study entry were continued unchanged. Two subjects receiving placebo dropped out early due to worsening or non-adherence to the protocol. Among the 22 subjects who completed the trial, six (50%) of the inositol-treated subjects responded with a 50% or greater decrease in the baseline Hamilton Depression Rating Scale (HAM-D) score and a Clinical Global Improvement (CGI) scale score change of 'much' or 'very much' improved, as compared to three (30%) subjects assigned to placebo, a statistically nonsignificant difference. On the Montgomery-Asberg Depression Rating Scale (MADRS), eight (67%) of twelve inositol-treated subjects had a 50% or greater decrease in the baseline MADRS scores compared to four (33%) of twelve subjects assigned to placebo (p = 0.10). Inositol was well tolerated with minimal side effects, and thymoleptic blood levels were unaltered. These pilot data suggest a controlled study with an adequate sample size, and the appropriate rating scale may demonstrate efficacy for inositol in bipolar depression. The tolerability and the 'natural substance' aspect of inositol may be particularly appealing to subjects with bipolar depression.

Higgins JPT, Thompson SGQuantifying heterogeneity in a meta-analysis. Stat Med 21: 1539-1558

Article

Jun 2002

The extent of heterogeneity in a meta-analysis partly determines the difficulty in drawing overall conclusions. This extent may be measured by estimating a between-study variance, but interpretation is then specific to a particular treatment effect metric. A test for the existence of heterogeneity exists, but depends on the number of studies in the meta-analysis. We develop measures of the impact of heterogeneity on a meta-analysis, from mathematical criteria, that are independent of the number of studies and the treatment effect metric. We derive and propose three suitable statistics: H is the square root of the chi2 heterogeneity statistic divided by its degrees of freedom; R is the ratio of the standard error of the underlying mean from a random effects meta-analysis to the standard error of a fixed effect meta-analytic estimate, and I2 is a transformation of (H) that describes the proportion of total variation in study estimates that is due to heterogeneity. We discuss interpretation, interval estimates and other properties of these measures and examine them in five example data sets showing different amounts of heterogeneity. We conclude that H and I2, which can usually be calculated for published meta-analyses, are particularly useful summaries of the impact of heterogeneity. One or both should be presented in published meta-analyses in preference to the test for heterogeneity.

.Myo-inositol has no beneficial effect on premenstrual dysphoric disorder.

Article

Aug 2002

Inositol, a simple isomer of glucose, which serves as a precursor in the phosphatidyl-inositol (PI) second messenger cycle, was shown to be effective in double-blind, placebo-controlled studies of depression, panic and obsessive compulsive disorders as well as in bulimia. The following study was designed to investigate whether inositol has beneficial effects in another disorder shown to be responsive to SSRIs: premenstrual dysphoric disorder (PMDD). Eleven female patients with PMDD diagnosed according to DSM-IV participated in a cross-over, double-blind, placebo-controlled trial. The active drug was myo-inositol, 12 g daily, whereas placebo was d-glucose administered at the same dose. Each drug was given during the luteal phase only (14 days prior to menses). For each patient treatment alternated between these two drugs for six menstrual cycles. No beneficial effect was demonstrated for inositol over placebo.

The Assessment of Anxiety States By Rating

Article

Feb 1959
Br J Med Psychol

Max Hamilton

A Rating Scale for Depression

Article

Mar 1960

M. A. X. Hamilton

Inositol for depressive disorders

Article

Feb 2004

There are a number of effective interventions for the treatment of depression. It is possible that the efficacy of these treatments will be improved further by the use of adjunctive therapies such as inositol. 1. To determine the effectiveness of inositol in the treatment of depression.2. To determine the adverse effects and acceptability of treatment with inositol. The Cochrane Controlled Trials Register (CCTR), The Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (CCDANCTR) incorporating results of group searches of EMBASE, MEDLINE, LILACS, CINAHL, PSYNDEX and PsycLIT were searched. Reference lists of relevant papers and major textbooks of affective disorder were checked. Experts in the field and pharmaceutical companies were contacted regarding unpublished material. All randomised controlled trials that compare treatment with inositol, whether as monotherapy or adjunctive therapy, to an alternative treatment, whether another antidepressant medication or placebo, for patients with a diagnosis of depressive disorder (diagnosed according to explicit criteria). Data were independently extracted from the original reports by two reviewers. Statistical analysis was conducted using Review Manager version 4.2.1. Four trials were identified, with a total of 141 participants. These were short term trials of double-blind design. The trials did not show clear evidence of a therapeutic benefit, nor any evidence of poor acceptability. It is currently unclear whether or not inositol is of benefit in the treatment of depression. Ongoing studies should reduce this uncertainty.

Decreased Prefrontal Myo-Inositol in Major Depressive Disorder

Article

Jul 2005
BIOL PSYCHIAT

Postmortem studies have shown robust prefrontal cortex glial losses and more subtle neuronal changes in major depressive disorder (MDD). Earlier proton magnetic resonance spectroscopy (1H-MRS) studies of the glial marker myo-inositol in MDD were subject to potential confounds. The primary hypothesis of this study was that MDD patients would show reduced prefrontal/anterior cingulate cortex levels of myo-inositol. Thirteen nonmedicated moderate-severe MDD patients and 13 matched control subjects were studied (six male, seven female per group). Proton magnetic resonance spectroscopy stimulated echo acquisition mode spectra (3.0 T; echo time=168 msec; mixing time=28 msec; repetition time=3000 msec) were obtained from prefrontal/anterior cingulate cortex. Metabolite data were adjusted for tissue composition. Patients with MDD showed significantly lower myo-inositol/creatine ratios (.94+/-.23) than control subjects (1.32+/-.37) [F(1,23)=6.9; p=.016]. These data suggest a reduction of myo-inositol in prefrontal/anterior cingulate cortex in MDD, which could be a consequence of glial loss or altered glial metabolism. Additional in vivo studies of glial markers could add to the understanding of the pathophysiology of MDD.

Inositol augmentation of lithium or valproate for bipolar depression

Article

Apr 2006

Despite promising new therapies, bipolar depression remains difficult to treat. Up to half of patients do not respond adequately to currently approved treatments. This study evaluated the efficacy of adjunctive inositol for bipolar depression. Seventeen participants with DSM-IV criteria for bipolar depression and a 17-item Hamilton Rating Scale for Depression (HRSD) > or =15 on proven therapeutic levels of lithium or valproate for >2 weeks were randomized to receive double-blind inositol or placebo for 6 weeks. At the end of double-blind treatment, subjects were eligible for an 8-week open-label trial of inositol. Response was defined a priori as >50% reduction in the HRSD and a Clinical Global Impression of 1-2. Four of nine subjects (44%) on inositol and zero of eight subjects on placebo met response criteria (p = 0.053). There was no difference between groups in the average change score for the HRSD or Young Mania Rating Scale (YMRS). Response to inositol was highly variable. Of nine subjects randomized to inositol, two had >50% worsening in HRSD scores at the end of treatment, three had no change and four had >50% improvement. Those who had worsening in depressive symptoms on inositol had significantly higher scores at baseline on the YMRS total score and irritability, disruptive/aggressive behavior and unkempt appearance items. There was a trend for more subjects on inositol to show improvement in bipolar depression symptoms, but, on average, inositol was not more effective than placebo as an adjunct for bipolar depression. Baseline levels of anger or hostility may be predictive of clinical response to inositol.

Jan 2004
55-63

Mj Taylor
H Wilder
Z Bhagwagar
Geddes

Taylor MJ, Wilder H, Bhagwagar Z, Geddes J. 2004. Inositol for depressive disorders. Cochrane database of systematic reviews.:CD004049. 63 inositol and depression and anxiety disorders Copyright © 2013 John Wiley & Sons, Ltd. Hum. Psychopharmacol Clin Exp 2014; 29: 55–63.

Manual for the ECDEU Assessment Battery Chevy Chase, Md, National Institute of Mental Health. Hamilton M. 1959. The assessment of anxiety states by rating

Jan 1970
50-55

Guy W Bonato

Guy W, Bonato RR. 1970. Manual for the ECDEU Assessment Battery, 2nd ed. Chevy Chase, Md, National Institute of Mental Health. Hamilton M. 1959. The assessment of anxiety states by rating. Br J Med Psychol 32: 50–55.

Myo-inositol has no beneficial effect on premenstrual dysphoric disorder. The world journal of biological psychiatry: the official journal of the World Federation of Societies of

Jan 2002
147-149

Nemets B B Talesnick
Rh Belmaker
Levine

Nemets B, Talesnick B, Belmaker RH, Levine J. 2002. Myo-inositol has no beneficial effect on premenstrual dysphoric disorder. The world journal of biological psychiatry: the official journal of the World Federation of Societies of Biological Psychiatry 3: 147–149.

Manual for the ECDEU Assessment Battery

W Guy
Rr Bonato

Inositol for depressive disorders. Cochrane database of systematic reviews

Mj Taylor
H Wilder
Z Bhagwagar
J Geddes

Inositol for depressive disorders. Cochrane database of systematic reviews

Taylormj Wilderh Bhagwagarz Geddesj

A meta-analysis of inositol for depression and anxiety disorders

Abstract

No full-text available

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