Omega-3 Polyunsaturated Fatty Acids in Prevention of Mood and Anxiety Disorders

Su, Kuan-Pin,Matsuoka, Yutaka,Pae, Chi-Un Korean College of Neuropsychopharmacology 2015 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.13 No.2

<P>Psychiatric disorders in general, and major depression and anxiety disorders in particular, account for a large burden of disability, morbidity and premature mortality worldwide. Omega-3 polyunsaturated fatty acids (PUFAs) have a range of neurobiological activities in modulation of neurotransmitters, anti-inflammation, anti-oxidation and neuroplasticity, which could contribute to psychotropic effects. Here we reviewed recent research on the benefits of omega-3 PUFA supplements in prevention against major depression, bipolar disorders, interferon-<I>α</I>-induced depression patients with chronic hepatitis C viral infection, and posttraumatic stress disorder. The biological mechanisms underlying omega-3 PUFAs’ psychotropic effects are proposed and reviewed. Nutrition is a modifiable environmental factor that might be important in prevention medicine, which have been applied for many years in the secondary prevention of heart disease with omega-3 PUFAs. This review extends the notion that nutrition in psychiatry is a modifiable environmental factor and calls for more researches on prospective clinical studies to justify the preventive application of omega-3 PUFAs in daily practice.</P>

Targeting Three Brain Regions (Bilateral SMA, Left and Right DLPFC) Sequentially in One Session Using Combined Repetitive Transcranial Magnetic Stimulation and Intermittent Theta-burst Stimulation in Treatment-refractory Obsessive-compulsive Disorder: A

Po-Han Chou(Po-Han Chou),Alexander T. Sack(Alexander T. Sack ),Kuan-Pin Su(Kuan-Pin Su) 대한정신약물학회 2022 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.20 No.4

Repetitive transcranial magnetic stimulation (rTMS) has been widely used as a therapy for refractory obsessive-compulsive disorder (OCD). However, it remains unclear which exact target and stimulation sequence of rTMS is most effective for OCD. Here, we report the case of an 18-year-old female with treatment-refractory OCD whose symptoms markedly improved after combined rTMS and intermittent theta-burst stimulation over the bilateral dorsolateral prefrontal cortex and supplementary motor area. Our report indicates that combining treatment sequences that stimulate different brain regions sequentially is feasible and may clinically benefit patients suffering from OCD.

Nutritional Neuroscience as Mainstream of Psychiatry: The Evidence- Based Treatment Guidelines for Using Omega-3 Fatty Acids as a New Treatment for Psychiatric Disorders in Children and Adolescents

Jane Pei-Chen Chang,Kuan-Pin Su 대한정신약물학회 2020 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.18 No.4

Omega-3 polyunsaturated fatty acids (or omega-3 PUFAs, n-3 PUFAs) are essential nutrients throughout the life span. Recent studies have shown the importance of n-3 PUFAs supplementation during prenatal and perinatal period as a potential protective factor of neurodevelopmental disorders. N-3 PUFAs have been reported to be lower in youth with attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD) and major depressive disorder (MDD). N-3 PUFAs supplementation has shown potential effects in the improvement of clinical symptoms in youth with ADHD, ASD, and MDD, especially those with high inflammation or a low baseline n-3 index. Moreover, it has been suggested that n-3 PUFAs had positive effects on lethargy and hyperactivity symptoms in ASD. For clinical application, the following dosage and duration are recommended in youth according to available randomized controlled trials and systemic literature review: (1) ADHD: a combination of eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) ≥ 750 mg/d, and a higher dose of EPA (1,200 mg/d) for those with inflammation or allergic diseases for duration of 16−24 weeks; (2) MDD: a combination of a EPA + DHA of 1,000−2,000 mg/d, with EPA:DHA ratio of 2 to 1, for 12−16 weeks; (3) ASD: a combination of EPA + DHA of 1,300−1,500 mg/d for 16−24 weeks as add-on therapy to target lethargy and hyperactivity symptoms. The current review also suggested that n-3 index and inflammation may be potential treatment response markers for youth, especially in ADHD and MDD, receiving n-3 PUFA.

Deficiency or activation of peroxisome proliferator-activated receptor α reduces the tissue concentrations of endogenously synthesized docosahexaenoic acid in C57BL/6J mice

Hsiao, Wen-Ting,Su, Hui-Min,Su, Kuan-Pin,Chen, Szu-Han,Wu, Hai-Ping,You, Yi-Ling,Fu, Ru-Huei,Chao, Pei-Min The Korean Nutrition Society 2019 Nutrition Research and Practice Vol.13 No.4

BACKGROUND/OBJECTIVES: Docosahexaenoic acid (DHA), an n-3 long chain polyunsaturated fatty acid (LCPUFA), is acquired by dietary intake or the in vivo conversion of ${\alpha}$-linolenic acid. Many enzymes participating in LCPUFA synthesis are regulated by peroxisome proliferator-activated receptor alpha ($PPAR{\alpha}$). Therefore, it was hypothesized that the tissue accretion of endogenously synthesized DHA could be modified by $PPAR{\alpha}$. MATERIALS/METHODS: The tissue DHA concentrations and mRNA levels of genes participating in DHA biosynthesis were compared among $PPAR{\alpha}$ homozygous (KO), heterozygous (HZ), and wild type (WT) mice (Exp I), and between WT mice treated with clofibrate ($PPAR{\alpha}$ agonist) or those not treated (Exp II). In ExpII, the expression levels of the proteins associated with DHA function in the brain cortex and retina were also measured. An n3-PUFA depleted/replenished regimen was applied to mitigate the confounding effects of maternal DHA. RESULTS: $PPAR{\alpha}$ ablation reduced the hepatic Acox, Fads1, and Fads2 mRNA levels, as well as the DHA concentration in the liver, but not in the brain cortex. In contrast, $PPAR{\alpha}$ activation increased hepatic Acox, Fads1, Fads2, and Elovl5 mRNA levels, but reduced the DHA concentrations in the liver, retina, and phospholipid of brain cortex, and decreased mRNA and protein levels of the brain-derived neurotrophic factor in brain cortex. CONCLUSIONS: LCPUFA enzyme expression was altered by $PPAR{\alpha}$. Either $PPAR{\alpha}$ deficiency or activation-decreased tissue DHA concentration is a stimulus for further studies to determine the functional significance.

Deficiency or activation of peroxisome proliferator-activated receptor ⍺ reduces the tissue concentrations of endogenously synthesized docosahexaenoic acid in C57BL/6J mice

Wen-Ting Hsiao,Hui-Min Su,Kuan-Pin Su,Szu-Han Chen,Hai-Ping Wu,Yi-Ling You,Ru-Huei Fu,Pei-Min Chao 한국영양학회 2019 Nutrition Research and Practice Vol.13 No.4

BACKGROUND/OBJECTIVES: Docosahexaenoic acid (DHA), an n-3 long chain polyunsaturated fatty acid (LCPUFA), is acquired by dietary intake or the in vivo conversion of α-linolenic acid. Many enzymes participating in LCPUFA synthesis are regulated by peroxisome proliferator-activated receptor alpha (PPARα). Therefore, it was hypothesized that the tissue accretion of endogenously synthesized DHA could be modified by PPARα. MATERIALS/METHODS: The tissue DHA concentrations and mRNA levels of genes participating in DHA biosynthesis were compared among PPARα homozygous (KO), heterozygous (HZ), and wild type (WT) mice (Exp I), and between WT mice treated with clofibrate (PPARα agonist) or those not treated (Exp II). In ExpII, the expression levels of the proteins associated with DHA function in the brain cortex and retina were also measured. An n3-PUFA depleted/replenished regimen was applied to mitigate the confounding effects of maternal DHA. RESULTS: PPARα ablation reduced the hepatic Acox, Fads1, and Fads2 mRNA levels, as well as the DHA concentration in the liver, but not in the brain cortex. In contrast, PPARα activation increased hepatic Acox, Fads1, Fads2, and Elovl5 mRNA levels, but reduced the DHA concentrations in the liver, retina, and phospholipid of brain cortex, and decreased mRNA and protein levels of the brain-derived neurotrophic factor in brain cortex. CONCLUSIONS: LCPUFA enzyme expression was altered by PPARα. Either PPARα deficiency or activation-decreased tissue DHA concentration is a stimulus for further studies to determine the functional significance.

Haloperidol and Other Antipsychotics Exposure before Endometrial Cancer Diagnosis: A Population-based Case-control Study

Wei-Ling Chen,Srinivasan Nithiyanantham,Yan-Chiao Mao,Chih-Hsin Muo,Chih-Pin Chuu,Shih-Ping Liu,Min-Wei Huang,Kuan-Pin Su 대한정신약물학회 2022 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.20 No.3

Objective: Endometrial cancer is the most common malignancy of the female genital tract worldwide, and the associated relationship between endometrial cancer formation and various antipsychotics need to be confirmed. Methods: We conducted a case-control study by using data from Taiwan National Health Insurance Research Database to compare individual antipsychotic exposure between females with and without endometrial cancer. Among 14,079,089 females in the 12-year population-based national dataset, 9,502 females with endometrial cancer were identified. Their medical records of exposure to antipsychotics, including quetiapine, haloperidol, risperidone, olanzapine, amisulpride, clozapine, and aripiprazole, for up to 3 years before endometrial cancer diagnosis were reviewed. Daily dosage and cumulative exposure days were analyzed in the risky antipsychotic users. Additionally, the subsequent 5-year mortality rate of endometrial cancer among users of the risky antipsychotic were also analyzed. Results: Among endometrial cancer patients, the proportion of those who have used haloperidol before being diagnosed with endometrial cancer is significantly higher than other antipsychotic users. The significant odds ratio (OR) and a 95% confidence interval of 1.75 (1.31−2.34) were noted. Furthermore, haloperidol users were associated with a significantly higher 5-year mortality rate after getting endometrial cancer than non-users. Conclusion: There is a high correlation between the use of haloperidol and endometrial cancer formation. However, the underlying pathological biomechanisms require additional investigations.

Gastrodia elata Bl. Attenuated Learning Deficits Induced by Forced-Swimming Stress in the Inhibitory Avoidance Task and Morris Water Maze

Pei-Ju Chen,Keng-Chen Liang,Hui-Chen Lin,Ching-Liang Hsieh,Kuan-Pin Su,Mei-Chu Hung,Lee-Yan Sheen 한국식품영양과학회 2011 Journal of medicinal food Vol.14 No.6

This study adopted the forced-swimming paradigm to induce depressive symptoms in rats and evaluated the effects on learning and memory processing. Furthermore, the effects of the water extract of Gastrodia elata Bl., a well-known Chinese traditional medicine, on amnesia in rats subjected to the forced-swimming procedure were studied. Rats were subjected to the forced-swimming procedure, and the inhibitory avoidance task and Morris water maze were used to assess learning and memory performance. The acquisition of the two tasks was mostly impaired after the 15-minute forced-swimming procedure. Administration of the water extract of G. elata Bl. for 21 consecutive days at a dosage of 0.5 or 1.0 g/kg of body weight significantly improved retention in the inhibitory avoidance test, and the lower dose showed a better effect than the higher one and the antidepressant fluoxetine (18 mg/kg of body weight). In the Morris water maze, the lower dose of the water extract of G. elata Bl. significantly improved retention by shortening escape latency in the first test session and increasing the time in searching the target zone during the probe test. These findings suggest that water extracts of G. elata Bl. ameliorate the learning and memory deficits induced by forced swimming.

Bupropion for Interferon-Alpha-Induced Depression in Patients with Hepatitis C Viral Infection: An Open-Label Study

Wei-Chun Chen,Hsueh-Chou Lai,Wen-Pang Su,Mahalakshmi Palani,Kuan-Pin Su 대한신경정신의학회 2015 PSYCHIATRY INVESTIGATION Vol.12 No.1

Interferon (IFN)-α therapy for chronic hepatitis C virus (HCV) infection is frequently associated with major depressive episodes. Bupropion, a commonly used antidepressant agent, has recently found to have strong anti-inflammatory effects in animal models. Despite of the theoretical relevancy, the antidepressant effect of bupropion in IFN-alpha-induced depression has never been studied. Ten HCV patients with IFN-α-induced depression were recruited to receive 8-week bupropion treatment and were assessed every 2 weeks for depressive symptoms by the Hamilton rating scale for depression (HAMD) and somatic symptoms by the Neurotoxicity Rating Scale (NRS). Four of the 10 patients met the criteria for remission (total HAMD scores≤7), and 5 patients met the criteria for response (at least 50% reduction in total HAMD scores). In addition, 5 patients had 50% decreases in NRS for neuropsychiatric symptoms. This preliminary open-label study suggests that bupropion is effective in treating IFN-alpha-induced depressive and somatic symptoms.

Personalization of Repetitive Transcranial Magnetic Stimulation for the Treatment of Major Depressive Disorder According to the Existing Psychiatric Comorbidity

Po-Han Chou,Yen-Feng Lin,Ming-Kuei Lu,Hsin-An Chang,Che-Sheng Chu,Wei Hung Chang,Taishiro Kishimoto,Alexander T. Sack,Kuan-Pin Su 대한정신약물학회 2021 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.19 No.2

Repetitive transcranial magnetic stimulation (rTMS) and intermittent theta-burst stimulation (iTBS) are evidenced-based treatments for patients with major depressive disorder (MDD) who fail to respond to standard first-line therapies. However, although various TMS protocols have been proven to be clinically effective, the response rate varies across clinical applications due to the heterogeneity of real-world psychiatric comorbidities, such as generalized anxiety dis-order, posttraumatic stress disorder, panic disorder, or substance use disorder, which are often observed in patients with MDD. Therefore, individualized treatment approaches are important to increase treatment response by assigning a given patient to the most optimal TMS treatment protocol based on his or her individual profile. This literature review summarizes different rTMS or TBS protocols that have been applied in researches investigating MDD patients with certain psychiatric comorbidities and discusses biomarkers that may be used to predict rTMS treatment response. Furthermore, we highlight the need for the validation of neuroimaging and electrophysiological biomarkers associated with rTMS treatment responses. Finally, we discuss on which directions future efforts should focus for developing the personalization of the treatment of depression with rTMS or iTBS.