Psychiatry
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Fish, fish oil, and omega-3 fatty acids are probably even more important for the brain and to prevent psychiatric illness than for heart disease where every American is urged to eat fish twice a week or take a supplement.  One to two fish oil capsules a day is plenty for the average person and three a day for anyone suffering from psychiatric difficulties.

Fish Oil Protects Against Mental Stress: A study of 7 normal adults given 7.2 g/d fish oil found after 3 weeks of a diet supplemented with n-3 fatty acids, the stimulation by mental stress of plasma epinephrine, cortisol, energy expenditure, and plasma non esterified fatty acids concentrations, were all significantly blunted. France. Fish oil prevents the adrenal activation elicited by mental stress in healthy men. Delarue J, Matzinger O, Binnert C, Schneiter P, Chiolero R, Tappy L. Diabetes Metab. 2003 Jun;29(3):289-95

Aggression

Fish Oil Decreases Aggression Under Stress in Normals: DB PC study of 41 Toyama, Japan young adults Rx capsules high in DHA 1.5-1.8g/d or soybean oil controls. Controls showed incr aggression during high stress period of study (exams, etc) while DHA group did not. Hamazaki, Toyama U, J Clin Invest 2/96;97:1129; Hamazaki, DHA on aggression in 53 non-smoking young Japanese adults found no increase in aggression on DHA 1.8g/day against other while placebo had a 9% increase during times of high stress after taking capsules for 3 months. J Clin Invest 1996; 97:1129-33

No Impact Fish Oil on Aggression Feelings in Normals Without Stress: DB PC study of 46 college students without stress. No difference with or without fish oil. Hamazaki, Toyama U, Lipids 7/98;33:663

Depression

Higher Fish Consumption by Nation Lowers Bipolar Disease, But Not Schizophrenia: A new study has shown that the more seafood consumed in a country, the lower the rates of bipolar disease. Below 50 pounds consumption of seafood per year seemed to be a threshold level below which risk of bipolar II and bipolar spectrum disorder increased.  Authors attribute the benefit to higher omega-3 fatty acid consumption. Cross-national comparisons of seafood consumption and rates of bipolar disorders. Noaghiul S, Hibbeln JR. Am J Psychiatry. 2003 Dec;160(12):2222-7. 

Omega-3 Low in Dutch Depressed: As part of the Rotterdam heart study, 3884 adults were screened for depression. 264 with depressive symptoms, including 106 with depressive disorders, and 461 random controls studied.  Depressed subjects with normal CRP concentrations (< 1.5 mg/L) had a substantially altered fatty acid composition; percentages of n-3 PUFAs and ratios of n-6 to n-3 PUFAs were significantly lower and higher, respectively, in subjects with depressive disorders than in control subjects [5.2% compared with 5.9% (P = 0.02) and 7.2 compared with 6.6 (P = 0.01), respectively]. Differences not due to inflammation or atherosclerosis. Suggests direct effect on mood. Plasma fatty acid composition and depression are associated in the elderly: the Rotterdam Study. Tiemeier H, van Tuijl HR, Hofman A, Kiliaan AJ, Breteler MM. Am J Clin Nutr. 2003 Jul;78(1):40-6

Omega-3 Low in Suicide Attempters: Hibbeln found non-depressed have high blood EPA and strikingly lower scores on 6 psych rating scales related to suicide risk. Another study = diet of EPA and DHA may influence serotonin function in brain. Synatic membranes have large proportion essential fatty acids which derive entirely from the diet. In the last century, western diet much less omega-3 and big increase in depression. The author links fish consumption by country with the level of depression. (NY Reuters 9/3/98) (Hibbeln may be prone to exaggeration, but he has brought attention to this important issue.)

Less Fish, More Depression in Finland: Large study found people who ate fish less than once a week had 31% more depression than those who ate more. Antti Tanskanen, U Kuopio, Chic AP 5/17/00. Finnish study of 3024 adults found higher fish intake linked to lower Beck Depression Inventory scores. Psychiatr Serv 2001 Apr;52(4):529-31. Suicidality also decreased. Frequent fish consumer considered twice a week or more. OR 0.63 for being depressed (BDI>10) and 0.57 for suicidal thoughts.

Less Post-Partum Depression with Higher Fish and Higher Breast Milk DHA: Published prevalence data for postpartum depression were included that used the Edinburgh Postpartum Depression Scale (n=14532 subjects in 41 studies). These data were compared to the DHA, eicosapentaenoic acid (EPA) and arachidonic acid (AA) content in mothers' milk and to seafood consumption rates in published reports from 23 countries. RESULTS: Higher concentrations of DHA in mothers' milk (r=-0.84, p<0.0001, n=16 countries) and greater seafood consumption (r=-0.81, p<0.0001, n=22 countries) both predicted lower prevalence rates of postpartum depression in simple and logarithmic models, respectively. The AA and EPA content of mothers' milk were unrelated to postpartum depression prevalence. J Affect Disord 2002 May;69(1-3):15-29, Hibbelm, NIAAA

More Fish, Less Depression for Japanese: Study of 265,000 with 17 yr f/u found those with daily fish intake decreased suicide. (Hirayama T. Life-Style and Mortality: A Large Census-Based Cohort Study in Japan. Basel, Switzerland: Karger, 1990.

More Fish, Less Seasonal Affective Disorder: Iceland has far lower rates of Seasonal Affective Disorder than expected based on latitude. Some think the decrease is due to high fish intake. Am J Psychiatry 2000;157:234-8 & 2001;158:328. (SAD has depression with hypersomnia and weight gain).

Omega-3 Depleted in Depr. Membrane lipid abnormalities occur in major depression. Curr Opinion in Psychiatry 10:477-80 11/97 Malcolm Peet. 10 depressed vs. 14 controls found depletion n-3 PUFAs in RBC membr and decr dietary intake with severity of depression correlated negatively. J Affect Disord 1998 Mar;48:149-55, Edwards R, Peet M, U Sheffield. RBC membr 6 tended to increase risk. Joel Simon, Am J Epid 9/1/95;142:469-76%. High n6 in depressives show evidence oxidative damage and n3 may be protective. Peet M, Biol Psychiatry 1998 Mar;43:315-9. Maes M of U Antwerp in J Affect Disord 1996 Apr; 38:35-46 found shift fr n3 to n6 in serum cholesteryl esters and phopholipids of 36 depressed vs. 14 minor depressed and 24 normals. Also Adams PB of Queensland in Lipids 1996 Mar;31 Suppl:S157-61 found 20 depressed with RBC arachidonic acid (AA) to EPA ratio increased with depression. But Ohio State med students showed more stress and less esterified AA and linoleic acid than control lab workers. Low AA could be from depletion of plasma stores by immunoreg prostenoids or cytokines. No diff n3 DHA. In Prostaglandins Leukot Essent Fatty Acids 1992 Oct;47:165-70.

Fish Intake Negatively Correlates with Depression around the world according to Jos R Hibbeln at NIH. Japanese, the nationality who eat the most fish, are least depressed. Says humans evolved on 1:1 diet n-6:n-3. Speculate depressions which accoompany alcoholism, MS, and postpartum depression may be due to lack of DHA and can be corrected by dietary DHA or linolenic acid as in flax. Am J Clin Nutr 7/95;62:1-9.

DB Omega-3 Helps M-D: Andrew Stoll of Harvard found omega-3 fatty acids improved symptoms of manic depression in 64% of 14 Pt after 4 mo. Vs. 18% of 16 on olive oil placebo. (USA Weekend 1/3/99). Rx 7BID high omega-3 fish oil capsules (440 EPA 240 DHA) per day (9.6 g/d) along with routine anti-manic and anti-depressant meds. Benefit apparent for both depr and manic symptoms. In press Arch Gen Psych. Four patients Rx with no psych meds but fish oil did well vs. 3-4 on olive oil who did poorly.

Stoll has used flax oil in open-label. Starting dose=5g/d of omega-3 or alpha-linolenic with max dose to date 15 g/d. at over 10 g/d some diarrhea and oily stools. If most fish oil HS, decr aftertaste. Also can put fish oil in OJ. Perilla oil less GI distress. Most fish oil caps only 300 mg omega-3 so need 32 caps/d to equal study level. If flax seeds, 4 Tablespoons of 17.5 g flax oil = 9.6 g omega-3 equivalent. If flax oil caps, start with 10/d and 17.5/d=9.6 g.

Lithium & valproate inhib neuronal signal transduction systems. Overactive cell-signal pathways may be pathophysiol of bipolar. High omega-3 dampens signal transduction assoc with phosphatidylinosital, arachidonic acid, and other systems. Study found benefit both depr and manic symptoms. High drop out in olive oil group and almost none from omega-e group. Rapid cycling and type I and II all did well tho numbers were small. 61% mild GI with omega-3 and 53% with olive oil. HAM-D decr 48% in omega-3 but incr 24% in olive oil, Young Mania RS both groups showed big drop. CGI and GAS both considerable improved in omega-3 and some deterioration in olive oil. The two that deteriorated on omega-3 both had manic upswings.

Studies show high omega-3 diet incorp into RBCs membrane phospholipids crucial for cell-signaling. High omega-3 in membr phospholipds suppresses phosphatidylinosital-associated signal transduction. May make membr more resistant to hydrolysis by phospholipases reducing generation of second messenger diacylglycerol (DAG) and inositol triphosphate (IP3) and thus less activation of downstrean intracellular signaling molecules as protein kinase C and calcium ions. Omega-3 highly incorporated in neuronal phospholipids in animals. Thus, suppresses aberrant signal transduction pathways.

DB EPA Highly Beneficial for Depression: 4-week, parallel-group, double-blind addition of either placebo or E-EPA to ongoing antidepressant therapy. Seventeen of the patients were women, and three were men. RESULTS: Highly significant benefits of the addition of the omega-3 fatty acid compared with placebo were found by week 3 of treatment. Am J Psychiatry 2002 Mar;159(3):477-9, B Nemets, Ben Gurion U.

Decreased DHA with Depr: Less DHA in RBCs of Depr. Biol Psych 98 43:315-9.

More Recent Depr: Cohorts born before 1934 1/5 to 1/20 the level of depr as those after 1945 (Klerman & Weissman, 1989)(Ed: maybe due in part to incr bottle feeding?). In this century PUFA consumption has decreased and saturated increased. Omega-6 up and Omega-3 down. www.shef.ac.uk

Hyperactivity, Dyslexia, Dyspraxia

Omega-3, Vit E, and Omega-6 Supplement Mild Benefit in DB: 50 children with ADHD who also had thirst and skin problems suggesting a possible omega-3 deficiency were studied in a 4-month DB PC program with half taking a daily dose of 480 mg DHA, 80 mg EPA, 40 mg arachidonic acid (AA), 96 mg GLA, and 24 mg alpha-tocopheryl acetate and half on placebo. On only two of 16 measures was there a significant advantage to the supplemented group: conduct problems rated by parents (-42.7 vs. -9.9%, P = 0.05), and attention symptoms rated by teachers (14.8 vs. +3.4%, P = 0.03). A greater number of participants also showed improvement in oppositional defiant behavior (8 out of 12 vs. 3 out of 11, P = 0.02). Purdue. EFA supplementation in children with inattention, hyperactivity, and other disruptive behaviors. Stevens L, Zhang W, Peck L, Kuczek T, Grevstad N, Mahon A, Zentall SS, Arnold LE, Burgess JR. Lipids. 2003 Oct;38(10):1007-21.

Fish Oil Lowered Truacy, Improved Learning: Slices of bread smeared with a fish oil enriched spread can improve kids' spelling and stop them missing school. South African researchers have told an Australian scientific conference that primary school children who were given daily doses of fish oil as part of a study showed improved learning and memory. Marius Smuts, from the Nutritional Intervention Research Centre in South Africa, tracked the development of 355 children aged between six and nine. Half were given two slices of bread covered with 25 grams of spread enriched with fish oil but flavored with either chicken, curry or tomato sauce. The children were able to retain information better and were less inclined to take sick days. Another study also reported to the conference found Omega 3 supplements taken by primary school students in Thailand reduced the severity and duration of common illnesses. Researchers recommend at least 400mg of Omega 3 in their food each day, but most Americans don't even get half of this. 7/31/06 Congress of the International Society for the Study of Fatty Acids and Lipids in Cairns, Australia. BBC News.

Fish Oil Helps Dyslexia, Dyspraxia, & ADHD: Fail to catch balls best predictor dyslexia. (Dyspraxia=clumsy child syndrome). Fish oil incr reading scores in dyslexia 29% 2 mo & 89% in 5 mo (Swede study). Rx ADHD with fish oil with gd results (Brit study). ADHD kids m st lack ability convert f.a. to LCPs-lg chain polyunsat fatty acids. Jackie Stordy. U Surrey, Lancet. AAPN Newsfeed.

No Benefit DHA in DB: J Pediatr 2001 Aug;139(2):189-96. 63 ADHD 6-12yos Rx 4 months 345mg/d or placebo. DHA blood level 100% higher but no behavioral or subjective diffenence. Mayo

May Help Dyspraxia: Children with dyspraxia, problems with coordination, often have dyslexia and visual difficulties. Four month open trial of 15 children with fish oil, primrose, and thyme oil showed improvement. Am J Clin Nutr 1/00. Also in dyslexic adults, dark adaptation a common problem. In five, dark adaptation improved after one month DHA vs controls.

Less Incorporation n-3s: There is evidence of less incorporation of DHA and AA into cell membranes. Horrobin, Nova Scotia, Med Hypotheses 12/95;45:605

Low Omega-3 in ADHD: 53 6-12-year-old boys with ADHD vs 43 without. Boys with ADHD lower AA, EPA & DHA in blood. More freq symptoms of EFA deficiency=thirst (16 vs 45%), freq urination (7 vs 34%), dry hair (0 vs 13%), dandruff (0 vs 8%) and dry skin (5 vs 11%), and more asthma and ear infections. Higher % controls had been breast fed and breast fed longer (p<.0001). 21 of ADHD with EFA def. symptoms had even lower AA and DHA than those without. Boys with low Omega-6 have more colds but not more behav problems. . Laura Stevens, Purdue, Dept Food Sciences, Am J Clin Nutr 10/95;62:761-8. John Burgess Dept Food and Nutrition, Stone Hall, W Lafayette 47907-1264

Schizophrenia

Open Study with Fish Oil Patients Improved: 4 months study with fish oil 1 g and Vitamin C 500 mg and vitamin E 400 IU twice a day to 33 schizophrenic patients reported their PANSS and BPRS scores decreased over 4 months. Supplementation with a combination of omega-3 fatty acids and antioxidants (vitamins E and C) improves the outcome of schizophrenia. Arvindakshan M, Ghate M, Ranjekar PK, Evans DR, Mahadik SP. Schizophr Res. 2003 Aug 1;62(3):195-204. Pune, India (Ed: This is a poor quality study).

EPA Differences Due to Smoking or Dietary: A DB PC study of 72 schizophrenic patients found no difference in symptom severity related to 3 g/d EPA. Smokers had lower RBC EPA and DHA and lower dietary intake of ALA. "Prior reports of abnormalities of essential fatty acid metabolism among schizophrenic patients may have been an artifact of patients' smoking behavior and differences in dietary intake of omega-3 fatty acids." NIH, NIAAA. Smoking, gender, and dietary influences on erythrocyte essential fatty acid composition among patients with schizophrenia or schizoaffective disorder. Hibbeln JR, Makino KK, Martin CE, Dickerson F, Boronow J, Fenton WS. Biol Psychiatry. 2003 Mar 1;53(5):431-41

Lower DHA in Schiz RBCs: Fatty acid research in schizophrenia has demonstrated an altered cell membrane phospholipid metabolism. Erythrocyte membrane phospholipid composition closest reflects that of neuronal membranes. METHODS: (Poly)(un)saturated fatty acid concentrations were measured in the erythrocyte membranes of 19, consecutively admitted, medicated young schizophrenic patients and then compared with matched control subjects. Psychiatric symptomatology was rated with the Positive and Negative Symptom Scale and Montgomery-Asberg Depression Rating Scale. Because diet, hormones, and cannabis influence fatty acid metabolism, we included these factors in our study. RESULTS: The most distinctive findings concerned the omega-3 series: C22:5 omega-3, C22:6 omega-3 (docosahexaenoic acid), and the sum of omega-3 fatty acids were significantly decreased. Interestingly, C20:4 omega-6 (arachidonic acid) was not lowered. In the omega-9 series, higher levels of C22:1 omega-9 and lower levels its elongation product, C24:1 omega-9 (nervonic acid), were found. Interestingly, the other arm of the desaturation-elongation sequence of C18:1 omega-9, C20:3 omega-9, was lower in patients. The total omega-9 fatty acid levels were also lower in patients. CONCLUSIONS: Significant differences in erythrocyte fatty acid composition were found. The differences were not due to diet or hormonal status and could not be explained by the medication or cannabis use. No consistent pattern emerged from the different fatty acid abnormalities and the clinical symptom scores. Biol Psychiatry 2001 Mar 15;49(6):510-22

Case Report of Benefit for Schiz: Omega-3 fatty acids are long-chain, polyunsaturated fatty acids found in plant and marine sources. Unlike saturated fats, which have been shown to have negative health consequences, omega-3 fatty acids are polyunsaturated fatty acids that have been associated with many health benefits. Omega-3 fatty acids may prove to be efficacious in a number of psychiatric disorders. Mood disorders have been associated with abnormalities in fatty acid composition. Several lines of evidence suggest that diminished omega-3 fatty acid concentrations are associated with mood disorders. Clinical data are not yet available regarding omega-3 fatty acids in the treatment of major depression. However, one double-blind treatment trial has been conducted in bipolar disorder. Also, substantial evidence does exist supporting a potential role of omega-3 fatty acids in schizophrenia, although treatment data are needed. A case has been reported in which a patient with schizophrenia was successfully treated with omega-3 fatty acids. Controlled studies are necessary to explore the potential treatment of schizophrenia with omega-3 fatty acids. Omega-3 fatty acids may also be helpful in the treatment of dementia. Furthermore, omega-3 fatty acids may prove to be a safe and efficacious treatment for psychiatric disorders in pregnancy and in breastfeeding. Ann Clin Psychiatry 2000 Sep;12(3):159-65

May Help Depress & Schiz: Medline search was conducted in September 1999. RESULTS: Five papers have investigated omega-3 fatty acids levels in depression. One study used omega-3 fatty acids as an adjunctive therapy in bipolar disorder. Four studies used fatty acids as an adjunctive therapy in schizophrenia. CONCLUSION: There is a great deal of current research in this field. While omega-3 fatty acids levels may be lowered in depression, there are no data suggesting that omega-3 fatty acids are effective. One paper indicates that omega-3 fatty acids are effective in bipolar disorders. The data on schizophrenia are conflicting. Omega-3 and omega-6 fatty acids have proved effective. Most of the evidence suggests that the main effect is an improvement in negative symptoms. One recent study showed that omega-3 fatty acids had no effect on negative symptoms. Acta Psychiatr Scand 2000 Jul;102(1):3-11

EPA no Benefit: Am J Psychiatry 2001 Dec;158(12):2071-4. 87 pt DB 3 gr/day. NIMH

Fish Oil Helped at High Dose: Dietary supplementation for six weeks with 10 g per day of concentrated fish oil (MaxEPA) led to significant improvement in schizophrenic symptoms. Lipids 1996 Mar;31 Suppl:S163-5 Sheffield, UK

20% Brain Essential Fatty Acids, esp DFA Harv Ment Health Lett 2001 Oct;19(2):4-5

EPA Helps Schiz More Than DHA: 25% improvement in 3-mo trial vs DHA or placebo. Malcolm Peet, Sheffield, Eng (NY Reuters 9/3/98). Peet says depleted AA and DHA in RBC membr of schiz and and 1st degree relatives and improvement in schiz and TD in 6 mo open trial incr n-3. Pts continued on previous psych meds. Peet, PLEFA 8/96;55:71

Schiz Less Likely Breast Fed so Less EPA-DHA: Brit J Psychiatry study lack of breast milk increases the risk of schiz. More schizoid and schizotypal and lower IQ. Robin McCreadie, Scotland

n-3 Helps Schiz: DB study reported at Int Congress on Schiz Res 4/97 that adding n-3 to Rx results in improvement. Peet, Laugharne.

Negative Symptoms Improve in Schiz: Chronic schiz with negative flush test found incr flush after 6 mo. EFA supplementation and improvement in affective symptoms. Glen, UK, Prostogl Leuko EFA 8/96;55:9. Pts without flush had low DHA and AA.

Diet in 8 Countries: Study found that 97% of the variance in patient recovery between countries could be attributed to dietary variations with high total fat intake and high intake of land animal and bird fat especially. There is a favorable recovery linkage, tho not as strong, linked to a higher intake of fats from fish, seafood, and vegetables. Christiansen, Denmark, Acta Psychia Scand 88;78:587

Fish Oil Helps Schiz: Laugharne of Sheffield found 10 caps of fish oil/d led to signif improvement mental function. RBC deficiency in both n-3 and n-6 esp DHA and arachidonic acid. No deficiency in diets tho indiv with higher n-3 in diet not as severe. Lipids /96

Schiz Skin Fibroblacts Abn: S. Mahadik in Prostagl Leukot EFA 55:65-70 96 and Psychiatry Res 63:133-42 notes earlier reports of defectin utilization of Essential PUFAs by RBCs. Cultered skin fibroblasts. Uptake and incorp of both LA and ALA were normal. The utilization of EPA into DHA was significantly lower in 1st-episode psychotic patients (96 vs 161 nmoles/mg) indicating delta 6- and delta 5-desaturase may be normal but delta 4 may be lower in fibroblasts from 1st episode patients. Ramchand & Peet in 55:59-64 say abn decr tyrosine transport has been documented in two studies of schiz fibroblast cultures and that it has been shown that tyrosine transport into the brain is also decreased. They say they have also found a decr for tyrosine transport in schiz fibroblasts and that the inhibition is uncompetitive. They suggest a cell membrane problem, one that could be due to altered metabolism of phospholipids such as AA and DHA

Schiz with Abn RBC Membranes: 40 Schiz pts tested and found incr frequency of dihomogamma-linolenic acid but no abn phospholipase-A2 allele. Doris, UK Schiz Res 5/98 31:185. Vaddadi in Schiz Res 7/96;20:287 also found incr in RBC dihomogamma-linolenic and also a decr in linoleic in 72 schiz. No relationship to TD. Horrobin 96 Prostag Leuk EFA 55:3-7 says schiz is disorder of membrane phospholipid metab assoc with loss of highly polyunsat f.a. from membr due to enhanced activiy of a phospholipase A2. M

Incr n-3 Membrane Loss in Schiz: Evidence for enhanced phospholipase A2 activity causing a loss of EPA and DHA from membranes. Horrobin, Nova Scotia, Med Hypotheses 12/95;45:605

Helps Schiz in Case Report: Notes inverse relationship betw schiz and some inflam disorders. Increased risk assoc with maternal malnutrition during fetal development. Differences is severity and prognosis in different countries (Horrobin Schiz Res 94;13:195@Notes studies findin membr def of AA and DHA from excess activity of phospholipase A2. Clozapine assoc with dramatic rise in RBC membr PUFAs. EPA a PLA2 inhibitor. Rx 2g/d EPA. Dramatic improvement esp betw 1st and 2nd month with continuing good rate betw 2nd and 3rd month and slow continuing improvement through 6th month where symptoms 80% gone. Contining improvement in second 6 months. Excessive activity of cytosolic PLA2 leads to depletion of AA and DHA. Basan Puri, London

Less Oxidative Damage with Anti-Psychotics: Sheffield study showing less oxidative damage to RBCs of schiz pts medicated with anti-psychotics suggesting a protective role and that the EFA deficits in schiz RBC are nt due to Rx but to schiz process. PLEFA 8/96;55:27

Failing Niacin Flush=Deficit AA & DHA: Schiz pts found that after 6 mo EPA Rx flush test improved. Glen, Vaddadi, Horrobin, Inverness, PLEFA 8/96

High Dose Phenothiazine/thioxanthene Lower EPA/DHA: Study of thrombocyte of low and high dose Rx of schiz and control found marked decr in AA, EPA, DHA, and ALA in high dose and AA in low dose. Fischer, U Munich, Biochem Pharmacol 2/92;44:317