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Depression: Causation & Risk Factor Studies

This is not a comprehensive listing, but rather articles I have come across. Genetics obviously plays a major role in serious, recurrent depression. Emotional losses, abuse, and violence are another factor.  Some medications can cause depression in small percentages of individuals, e.g. Accutane, fenfluramine, immunotherapy, and interferon.  Medical illnesses increase the risk of depression.  These include diabetes, hypertension, dementia, Wilson's disease, head trauma, multiple sclerosis, inflammatory disorders, obesity, Parkinson's disease, strokes, and pancreatic cancer. Marijuana and tobacco are causes of depression as is heavy alcohol drinking. Some abnormalities in blood tests have been found more often in the depressed including low folate, and high homocysteine.  Early teen sex, drugs, crime, and verbal, physical, and sexual abuse each increase the risk of depression.

Serotonin & Norepinepherine: Serotonin-containing nerve terminals primarily originate in the dorsal raphe nucleus located in the midbrain, and project throughout the forebrain, including the prefrontal cortex. Numerous approaches have suggested the involvement of HT circuit dysfunction in depression. Norepinephrine projections originate from a pontine brain region, the locus ceruleus (LC), and like the raphe neurons, these neurons project to the frontal cortex and limbic system. low levels of the major 5-HT metabolites have been detected in the cerebrospinal fluid (CSF) of depressed and suicidal patients. An increased density of 5-HT2 receptors has also been detected in both blood platelets and in the postmortem brain tissue of depressed patients.; rate of serotonin biosynthesis in male brains was 52% higher than that in female brains. low levels of NE metabolites have been measured in the urine and CSF of depressed patients. increased density of beta-adrenergic receptors has been observed in postmortem cerebral cortex of depressed suicide victims. Third, alpha2 adrenoreceptor sensitivity is apparently altered in depression, perhaps best exemplified by the blunted growth hormone response after administration of clonidine, an alpha2 agonist. selective NE reuptake inhibitors are effective antidepressants (i.e., desipramine, reboxetine, maprotiline). Modulation of brain serotonin levels effects impulsivity, and modulates sexual behavior, appetite, and aggression. Norepinephrine systems seem to directly modulate vigilance, socialization, energy, and overall motivation. Both systems also appear to modulate anxiety, irritability, pain, as well as modulating mood, emotion, and cognitive function.

Abuse Linked to Depression: In a study of Australian women, 18.0% (218/1213) of women scored as currently probably depressed and 24.1% (277/1147) had experienced some type of abuse in an adult intimate relationship. Depressed women were significantly more likely to have experienced severe combined abuse than women who were not depressed after adjusting for other significant sociodemographic variables (odds ratio 5.8). These variables included not being married, having a poor education, being on a low income, being unemployed or receiving a pension, pregnancy status, or being abused as a child. Association between depression and abuse by partners of women attending general practice: descriptive, cross sectional survey. Kelsey Hegarty. BMJ  3/13/2004;328:621-624. Ed: The same is very likely true for men, although this is rarely studied. Research shows men suffer as much verbal abuse in relationships as women with most of the abuse being mutual although in many relationships one partner is much more abusive than the other. Other research shows that verbal abuse is as damaging emotionally as physical abuse and is far more common. Having to live in an abuse situation is depressing and can have effects lasting even after no longer living in the abuse situation. 

Abuse Linked to Increased Depression in Women: In a prospective study of 905 New Zealanders followed from age 3 to 26, 37 men and 38 women had been subjected to partner abuse producing physical injuries.  While incidents of abuse were similar in both groups, battered women were more likely to have had depression, marijuana dependence while men had had alcohol dependence and anxiety prior to the onset of abuse.  Women in abusive relationships were more likely to suffer major depression and PTSD when compared to women not in abusive relationships. Ehrensaft MK, et al. Columbia Univ. J Psychiatry 5/06. In a random sample of 3568 women ages 18-64, 44% suffered partner abuse in the previous five years with one-third physically injured and 17% reported forced sexual contact. Thompson RS, et al. Amer J Preventive Med 6/06.

Accutane May Cause Depression: FDA reports may cause isolated cases depression, psychosis, suicide. Amer Health 4/98 p 22; FDA as of May 2000 431 cases depression or suicidal with isotretinoin and 37 deaths. However, FDA analysis says rate no higher than general population. Roche requires Informed Consent Agreement from patient. NEJM 01;344:460

Alcohol: Heavy Drinking Causes Depression and Vice-Versa: Using data are from the 2002 Canadian Community Health Survey: Mental Health and Well-being and the National Population Health Survey, an estimated 641,000 people (2.6% of adults) were dependent on alcohol, and 194,000 (0.8%), on illicit drugs. Heavy drinking more than once a week was a risk factor for a new episode of depression, and depression was a risk factor for new cases of frequent heavy drinking. Alcohol and illicit drug dependence. Tjepkema M. Statistics Canada, Toronto, Ontario. Health Rep. 2004;15 Suppl:9-19.

Alcohol: Moderate Use Doesn't Increase or Decrease Later Depression: In analyzing 2 waves of interview data from 13,892 young adults in the National Longitudinal Study of Adolescent Health, with adjustment for health and socioeconomic factors, the frequency of depressive symptoms was similar among moderate drinkers, lifetime and long-term abstainers, but remained significantly higher among heavy drinkers. Moderate alcohol use and depression in young adults: findings from a national longitudinal study. Paschall MJ, Freisthler B, Lipton RI. Berkeley, CA. Am J Public Health. 2005 Mar;95(3):453-7.

Alzheimers High Rate of Major Depressive Disorder: 243 probable AD patients studied. 22%-55% had MDD in the four AD clinics in study. A collaborative study of the emergence and clinical features of the major depressive syndrome of Alzheimer's disease. Zubenko GS, Zubenko WN, McPherson S, Spoor E, Marin DB, Farlow MR, Smith GE, Geda YE, Cummings JL, Petersen RC, Sunderland T. Am J Psychiatry. 2003 May;160(5):857-66

Amino Acid Dietary Intake Not Related to Depression: A very large and detailed Finnish study of over 29,000 men 50-69 yo over 5-8 years found no increase in depression or suicides in individuals consuming less of any particular amino acid. Association of dietary amino acids with low mood. Hakkarainen R, Partonen T, Haukka J, Virtamo J, Albanes D, Lonnqvist J. Depress Anxiety 2003;18(2):89-94

Arterial Rigidity Associated with Elderly Depression: Depressive symptoms were more often observed in subjects with increased arterial stiffness. For each standard deviation decrease in carotid distensibility, there was a 24% increased risk of depression; and for each standard deviation decrease in aortic pulse wave velocity, there was a 17% increased risk of depression. 3700 screened in Rotterdam. Erasmus U. J Am Geriatr Soc 2003;51:000-000.

Atypical Depression Defined by Overeating and Oversleeping: Interpersonal sensitivity and mood reactivity difficult to diagnose. Study of 400 MDD and bipolars found using only reverse vegetative symptoms defined virtually the same population. Can only reversed vegetative symptoms define atypical depression? Benazzi F. Eur Arch Psychiatry Clin Neurosci 2002 Dec;252(6):288-93

Atypical Depression: More Likely Bipolar, Female: 54% bipolar II vs 28% MDD found to be atypical depression by DSM-IV in study of 202 bipolar II and 282 MDD. Symptoms occurred together. Ann Clin Psychiatry. 2003 Mar;15(1):9-16

Beta-Blocker Anti-Hypertensive Medication: In a 1-year DB study of 1152 patients with coronary artery disease (CAD) and hypertension, among patients with a previous history of depression, depressive symptoms improved on both treatments. Depressive symptoms improved for patients with no depression history in the verapamil SR group (p < 0.001) and were unchanged in the atenolol group (p = 0.52). Patients assigned to the atenolol-based strategy without prior history of depression were more likely to worsen 5 or more points on the CES-D. Depressive Symptoms in Coronary Artery Disease Patients After Hypertension Treatment (April). Ried LD, et al. University of Florida Veterans Affairs Medical Center, Gainesville, FL. Ann Pharmacother 2006 Mar 28. Ed: Old epidemiologic studies long ago found that beta-blockers tend to increase depression. They may also be inferior anti-hypertensives in terms of longevity.

Brain: White Matter Hyperintensities in Frontal Periventricular Area Increased in Elderly Depression: In a study of 8 patients with heart failure and depression, 10 with heart failure alone, and 14 with neither. Braz J Med Biol Res. 2005 Mar;38(3):431-6.

Brain: Orbitofrontal Cortex Sometimes Damaged: The orbitofrontal cortex is involved in the monitoring of reward and in judgement. Lesion studies and functional neuroimaging investigations implicate this region in affective disorders, and altered neuronal and glial cell composition have been observed in this region in patients with major depressive disorder (MDD). In a study of 60 postmortem brains from patients with bipolar disorder (BPD), schizophrenia, MDD, and controls, researchers found a neuronal size reduction in BPD in layer 1 (21%, p=0.007) and a trend for a reduction in layer 5 (20%, p=0.05). There was a significant interaction effect of brain hemisphere and group on neuronal size in layer 3 (p=0.001), with evidence for reduced layer 3 neuronal sizes in MDD (30%, p<0.001). There were no group differences in glial cell size nor for differences in glial or neuronal density. There was no evidence for neuronal or glial pathology in this region in schizophrenia. Evidence for orbitofrontal pathology in bipolar disorder and major depression, but not in schizophrenia. Cotter D, et al. Dublin, Ireland. Bipolar Disord. 2005 Aug;7(4):358-69

Brain Injury Frequently Causes Depression: In a 12-month case-control study of 91 patients with traumatic brain injury (TBI) and 27 other multiple trauma victims without CNS injury, major depressive disorder was observed in 33% the first year after sustaining a TBI, significantly more frequent than among the controls. Patients with TBI who had major depression were more likely to have a personal history of mood and anxiety disorders than patients who did not have major depression. Patients with major depression had comorbid anxiety (77%) and aggressive behavior (57%). Major depression was also associated with poorer social functioning at the 6-and 12-month follow-up, as well as significantly reduced left prefrontal gray matter volumes, particularly in the ventrolateral and dorsolateral regions. Major depression following traumatic brain injury. Jorge RE, et al. University of Iowa. Arch Gen Psychiatry. 2004 Jan;61(1):42-50.

Breast-Feeding Protective Against Schizophrenia: In a study of 6841 adults from the Copenhagen Perinatal Cohort of whom 1671 (24%) had been breastfed for 2 weeks or less (early weaning) and 5170 (76%) had been breastfed longer, 93 developed schizophrenia (1.4%). Maternal schizophrenia was the strongest risk factor and a significant association between single mother status and elevated offspring risk of schizophrenia was also observed. Early weaning was significantly related to later schizophrenia (adjusted odds ratio 1.73). Breastfeeding and risk of schizophrenia in the Copenhagen Perinatal Cohort. Sorensen HJ, et al. Copenhagen University Hospital, Denmark. Acta Psychiatr Scand. 2005 Jul;112(1):26-9

Bullying May Markedly Increase Depression: 40 percent of girls who were frequently hit, kicked, threatened or called names said they were depressed and almost 25 percent said they thought about suicide. The numbers were only slightly lower when bullies used more indirect means -- such as ignoring, excluding and backbiting -- to torment their victims. Among girls who were often the target of indirect bullying, 35 percent said they were depressed and 21 percent said they had suicidal thoughts. Among girls who said they were almost never bullied directly, only about 6 percent reported depression and 4 percent said they thought about suicide. Effect present for boys as well in slightly smaller dimensions. van der Wal surveyed 4, 811 school children who were aged 9 to 13. Pediatrics 2003;111:1312-1317.

Bullying in Workplace Causes Depression: 5432 Finnish hospital employees. Outcomes were new reports of doctor diagnosed cardiovascular disease and depression 2 yr f/u: The prevalence of bullying was 5% in the first survey and 6% in the second survey. 2% bullying experiences in both surveys, an indication of prolonged bullying. After adjustment for sex, age, and income, the odds ratio of new cardiovascular disease for victims of prolonged bullying compared to non-bullied employees was 2.3. A further adjustment for overweight at baseline attenuated the odds ratio to 1.6. The association between prolonged bullying and incident depression was significant, even after these adjustments (odds ratio 4.2). Workplace bullying and the risk of cardiovascular disease and depression. Kivimaki M, Virtanen M, et al. Occup Environ Med. 2003 Oct;60(10):779-83

Cerebral Blood Flow Linked to Depression, Insomnia, Cognitive Performance: In a study of 15 patients with Major Depressive Disorder and off meds, single photon emission computed tomography (SPECT) showed that the severity of depressive mood was inversely correlated with the rate of cerebral blood flow (rCBF) in the left amygdala, lentiform nucleus, and parahippocampal gyrus, and directly correlated with rCBF in the right postero-lateral parietal cortex (p<0.001). Insomnia severity was inversely correlated with rCBF in the right rostral and subgenual anterior cingulate cortices, insula and claustrum. Anxiety severity was directly correlated with rCBF in the right antero-lateral orbitofrontal cortex, while cognitive performance was directly correlated with rCBF in the right postero-medial orbitofrontal cortex and in the left lentiform nucleus. Relationship between regional cerebral blood flow and separate symptom clusters of major depression: A single photon emission computed tomography study using statistical parametric mapping. Perico CA, Skaf CR, et al. University of Sao Paulo, Brazil. Neurosci Lett. 2005 May 24

Children of Depressed & Anxious Taken to Doctor’s More Quickly: Children whose mothers are the most depressed, anxious, and report high levels of psychosomatic symptoms are twice as likely to be taken to a doctor when they complain of a stomach ache or abdominal pain than are children whose mothers report the least amount of such mental stress. U Washington 3/28/03

Child Abuse Not as Important as Adult Abuse: A study of 1207 women in 13 medical clinics in London found that physical abuse during childhood was associated with increases in adult mental illness but that childhood sexual abuse had few connections.  However, the study found the more recent the abuse and the more intense, the more significant the effect.  Thus, domestic violence was the most important factor, especially violence in the past year was a major factor as was rape.  Abusive experiences and psychiatric morbidity in women primary care attenders. Coid J, Petruckevitch A, Chung WS, Richardson J, Moorey S, Feder G. Br J Psychiatry. 2003 Oct;183(4):332-339

Cholesterol Low, High Suicide: 11,500 adults were followed for 5 years. The lowest quartile in cholesterol level had six times the risk of highest quartile. Epid 3/2001, 12:168. Canadian retrospective study.

Cholesterol Lowering Not Affect Mood: In conclusion, cholesterol lowering did not negatively affect patients' moods. However, those who adhered poorly but nonetheless showed stable or reduced TC exhibited a greater decrease in anxiety. 212 obese on 1 year cholesterol lowering diet. Montreal, J Behav Med 2001 Dec;24(6):517-36

Cholesterol High in Treatment Resistant: Harvard. High = >or=200 mg/dl were significantly more likely to be nonresponders to fluoxetine. 59 SSRI treatment resistant patients had higher triglycerides. Those with high choles were less likely respond to nortriptyline in open trial. Serum cholesterol in treatment-resistant depression. Papakostas GI, Petersen T, Sonawalla SB, Merens W, Iosifescu DV, Alpert JE, Fava M, Nierenberg AA. Neuropsychobiology. 2003;47(3):146-51

Coffee Associated with Fewer Suicides: 86,626 RNs in a 10 year follow-up study showed markedly fewer suicides in those with increased coffee intake with 2-3 cups/day vs. none having a relative risk of just RR 0.34 which was unchanged after adjusting for many control factors. Kawachi, Harvard, Arch Intern Med ’96;156:521

Coffee or Tea Fewer Suicides: 128,934 persons to 4501 subsequent deaths. Except for slightly increased risk from acute myocardial infarction among heavier (> or = 4 cups/d) coffee users (relative risk versus nondrinkers = 1.4, 95% confidence interval = 1.0 to 1.9, P = 0.07), there was no increased risk of mortality for all deaths (relative risk per cup of coffee per day = 0.99, 95% confidence interval = 0.97 to 1.01; relative risk per cup of tea per day = 0.98, 95% confidence interval = 0.96 to 1.00) or major causes in adjusted analyses. Coffee was related to lower risk of liver cirrhosis death (relative risk per cup of coffee per day = 0.77, 95% confidence interval = 0.67 to 0.89). Use of both beverages was related to a lower risk of suicide, progressively lower at higher coffee intake (relative risk per cup of coffee per day = 0.87, 95% confidence interval = 0.77 to 0.98). We conclude that coffee and tea have no overall relation to mortality risk. Coffee, tea, and mortality. Klatsky AL, Armstrong MA, Friedman GD. Ann Epidemiol 1993 Jul;3(4):375-81

Critical Care Night Nurses Have High Rate of Depression: A Rutgers study of 143 critical care nurses drawn in a national random sample found 23% were clinically depressed, a very high rate. The levels of fatigue in day and night nurses was similar, but night-time critical care nurses suffered a higher rate of depression and sleep difficulties. Correlates of fatigue in critical care nurses. Ruggiero JS. Res Nurs Health. 2003 Dec;26(6):434-44

Diabetes: Depression Did Not Cause Poor Control, but Poor Control Had Higher Depression: In a 1-year prospective study of 1,665 Medicare diabetics (IDEATel), at baseline, there was a significant correlation between depression and A1C and a trend for depression to predict A1C when other factors were controlled. However, in prospective analyses, depression did not predict change in A1C, either in the control or intervention group. Depression and Glycemic Control in Elderly Ethnically Diverse Patients With Diabetes: The IDEATel Project. Trief PM, et al. SUNY Upstate Medical University. . Diabetes Care 2006 Apr;29(4):830-5.

Diabetes Under Poor Control Has More Depression: A Turkish study divided diabetes in two groups by their HbA1c >7% or not. Individuals with this indicator or poor control were almost twice as likely to be suffering from depression. Relationship between blood glucose control and psychiatric disorders in type II diabetic patients Eren I, Erdi O, Ozcankaya R. Turk Psikiyatri Derg. 2003 Fall;14(3):184-91

Diabetes Increased 63% by Depression: In a study of 11,615 adults followed for 6 years, the quarter with the most depressed symptoms were 63% more likely to develop diabetes type 2 than the quarter with the fewest symptoms. Sherita Hill Golden, Johns Hopkins. Diabetes Care 2/2004;27:429-435. Ed: Since magnesium protects against diabetes, the magnesium supplement in my standard recommendations (a multivitamin with minerals plus an extra 250mg magnesium once or twice a day) would likely prevent or at least reduce this risk.

Diabetes: Depressed Males Prone to Diabetes: In a study of 1,334 depressed and 66, 670 non-depressed adults, among males below age 50, but in not other groups, there was a 78% increase in the rate of development of DM compared with non-depressed patients (HR 1.78). Is depression related to subsequent diabetes mellitus? van den Akker M, Schuurman Aet al. Maastricht University, The Netherlands. Acta Psychiatr Scand. 2004 Sep;110(3):178-83. 

Diabetes: Depression Increases Diabetes Risk: In a 3-year follow-up study of 2,662 women, researchers found that depression was linked to higher insulin-resistance values and the onset of diabetes. This association resulted largely from abdominal obesity. Once the calculations were adjusted for "central adiposity," depression no longer predicted insulin resistance and diabetes -- except among African-American women. Diabetes was twice as high in African-American women at follow-up compared to European-American women. Susan A. Everson-Rose, Rush University Medical Center, Chicago, Diabetes Care, December 2004

Diabetes Gestational Type: Post-Partum Depression Increased; Treating Diabetes Lessens: In a follow-up random assignment study of 1000 women with diabetes developing gestational diabetes, i.e., diabetes during pregnancy which usually goes away after delivery, half with women had repeated blood sugar testing and counseling on diet. One-fifth received insulin as well. Half the women weren't told they had gestational diabetes and received only routine care. Three women in the untreated group had stillbirths and two newborns died vs. none with treatment. Half as many infants of the treated group weighed over 8.8 pounds. Only 1% of the treated vs. 4% of untreated had complications. Post-partum depression occurred in half as many of the treated women. CG Solomon, Brigham & Women's-Harvard. 6/16/05 NEJM. 

Drug Abuse: Early Smoking, Alcohol, Drugs, Sex, Crime Dramatically Increase Risk:  A population-based group of 578 male and 674 female twins reported whether they had ever engaged in, and the age of initiation of, five adolescent problem behaviors: smoking, alcohol use, illicit drug use, police trouble, and sexual intercourse. Participants also completed a structured interview at both ages 17 and 20 covering substance use disorders, major depressive disorder, and antisocial personality disorder. Each problem behavior was significantly related with each clinical diagnosis. The association was especially marked for those who had engaged in multiple problem behaviors before age 15. Among those with four or more problem behaviors before age 15, the lifetime rates of substance use disorders, antisocial personality disorder, and major depressive disorder exceeded 90%, 90%, and 30% in males and 60%, 35%, and 55% in females, respectively. Early adolescent problem behavior identifies a subset of youth who are at an especially high and generalized risk for developing adult psychopathology. The association of early adolescent problem behavior with adult psychopathology. McGue M, Iacono WG. University of Minnesota. Am J Psychiatry. 2005 Jun;162(6):1118-24. 

Fat: Depression and Anger Higher with Saturated Fat Intake is Very Small Study: In a study of 23 older adults enrolled in either an outpatient or in-residence executive health program, anxiety was negatively correlated with alcohol consumption. High levels of depression, trait anger, and outward anger expression style were positively associated with saturated fat intake. Trait anger was also associated with less aerobic exercise. Inward anger expression was positively correlated with regular participation in strength training. Results suggest that anger, anger expression style, and depression interact with healthy and unhealthy behavior patterns and that these interactions may be complex. Do negative emotions predict alcohol consumption, saturated fat intake, and physical activity in older adults? Anton SD, Miller PM. Medical University of South Carolina. Behav Modif. 2005 Jul;29(4):677-88.

Fenfluramine Diet pills Associated with Depression: An analysis of Canadian data found 0.5% of population in 1996 on diet pill fenfluramine and these report four times the level of major depression (17.1% vs. 4%). Can J Psychiatry 2001 Jun;46(5):438-40

Glial Difficiency in Depression: Patients with Major Depression or Bipolar with family members with the disorder as well had strikingly lower numbers of glial cells in a brain area implicated in depression, the subgenual prefrontal cortex. Thus, glial loss may play a role in mood disorders. Study was of 73 brain autopsies. Patients positive for the disorders but who had no family members with the disorders did not show the glial loss. Dost Ongur, Wash U, Proceedings of the Natl Acad of Science 10/27/98

Glial Brain Cell Dysfunction in Depression: Glial fibrillary acidic protein (GFAP) is a major protein of astrocyte intermediate filaments and a specific marker for astrocytes. GFAP levels in cerebella of 60 subjects divided equally among schizophrenia, bipolar disorder, major depression, and normal controls found levels were reduced by 32%, 17% and 14.5% in depressed, bipolar, and schizophrenic cerebella. Only the depressed value was significantly different (p=0.015). This adds to reports of reductions in GFAP/glial cell counts in other brain regions of subjects with major depression, thus suggesting a downregulation of glial function in this disorder. Glial fibrillary acidic protein is reduced in cerebellum of subjects with major depression, but not schizophrenia. Fatemi SH, Laurence JA, Araghi-Niknam M, Stary JM, Schulz SC, Lee S, Gottesman II. University of Minnesota. Schizophr Res. 2004 Aug 1;69(2-3):317-23

Green Eyed, Tremor, and Depressed: Wilson’s Disease affect 1 in 30,000. Due to a defect in a chromosome 13 gene for which 200 mutations have been found. Heterozygotes are minimally affected if at all. Onset between ages 10-40. Possible hepatitis, liver damage, tremor, slurred speech, lack of coordination, cramping, emotionality, depression, parkinsons, psychosis, and /or bizarre behavior. Low serum ceruloplasmin and high 24-hour urine copper for diagnosis. Kayser-Fleischer ring. Get liver enzymes. Rx chelation plus zinc which blocks copper absorption.

Hayfever May Increase Depression: In one study, of some 700 randomly selected children, those with hay fever were found to be twice as likely to develop a major depressive episode over the next few years than those without hay fever. In the other, of approximately 7,000 adults, those with hay fever were twice as likely to have been diagnosed with major depression within the previous year than those without hay fever. Third study found hayfever victims more depressed during hayfever season than control or during other seasons. Paula Marshall, July-August, 2002 Psychosomatic Medicine.

Head Trauma May Increase Depression: University of North Carolina surveyed 2,488 retired NFL players, with an average age of 58 and 6.7 years of playing pro football.  Those who had three or more concussions in their pro careers were nearly three times as likely to suffer clinical depression. 4/28/03 Am Assoc Neuro Surgeons, Kevin Guskiewicz

Heart Failure Damages Brain and Causes Depression: A UCLA imaging study revealed significant tissue loss in the regions of heart-failure patients' brains that regulate the autonomic nervous system, interfering with the cardiovascular system's ability to swiftly adapt to changes in blood pressure and heart rate. The damage lies in the same brain areas showing changes in people suffering major depression, which may explain why many heart-failure patients are often depressed. Mary Woo, et al. UCLA. J Cardiac Failure 8/2005:11(6)

Hepatitis C Treatment Increases Depression: Interferon-alpha (IFN-alpha) plus ribavirin is used to treat hepatitis C virus (HCV) infection and is associated with a high rate of depression. In a study of 162 HCV-infected patients at baseline and after 24 weeks of treatment with pegylated IFN alpha-2b (PEG IFN) plus weight-based (N = 86) versus standard dose (N = 76) ribavirin, 39% experienced moderate to severe depressive symptoms at some point during therapy. Baseline depression scores significantly predicted severity of depressive symptoms during PEG IFN/ribavirin treatment (p < .0001). In addition, assignment to weight-based ribavirin treatment increased depression risk 170% and history of depression increased the risk 230% (OR = 2.7, p < .01, and OR = 3.3, p < .01). Depression during pegylated interferon-alpha plus ribavirin therapy: prevalence and prediction. Raison CL, Borisov AS, et al. Emory University. J Clin Psychiatry. 2005 Jan;66(1):41-8.

Homocysteine: Depression Twice as High with High Homocysteine: In a cross-sectional study of 924 men ages 46-64 as a part of the Kuopio Ischemic Heart Disease Risk Factor Study (those with a history of psychiatric disorder (6.0%) were excluded), depressive symptoms were more than twice as high in individuals in the upper third for homocysteine levels (odds ratio: 2.30; P=0.002) vs. those in the lowest third. The results remained significant after adjustment for the month of study, history of ischemic heart disease, smoking habits, alcohol consumption, marital status, education, and socioeconomic status in adulthood (odds ratio: 2.23; P=0.004). Association between depressive symptoms and serum concentrations of homocysteine in men: a population study. Tolmunen T, Hintikka J, et al. University of Kuopio, Finland. Am J Clin Nutr. 2004 Dec;80(6):1574-8. Ed: High homocysteine can be corrected by folic acid and B-12 vitamins.

Immunotherapy Causes Depression; SSRI Helped: Depressive disorders occur in 12-30% of inflammatory disease patients, e.g., coronary heart disease and autoimmune diseases such as rheumatoid arthritis and inflammatory bowels. Immunotherapy used to treat patients who suffer either from kidney cancer or melanoma with metastasis, and, especially, from viral infections such as hepatitis C and AIDS causes depression in 33%. Immunotherapy involves the injections of cytokines, which are chemicals normally made by immune cells that boost the immune system to fight infectious pathogens and kill cancer cells. Depression begin within days to weeks of beginning treatment and often vanish once it ends. Cytokines may suppress serotonin by activating an enzyme called indoleamine-2,3-dioxygenase (IDO) that catabolizes tryptophan, an essential amino acid provided by ingested food. In the brain, IDO prevents tryptophan from being turned into serotonin, which causes decreased levels of serotonin and leads to the symptoms of depression (Dantzer, U Ill, Molecular PsychiatryI). Andrew Miler of Emory University found that the inexpensive SSRI fluoxetine (generic Prozac) lessens the level of depression in patients receiving immunotherapy. Dantzer, U Ill, Champaign. 7/29/04

Inflammatory Disease May Contribute to Depression: The genetically homogeneous Northern Finland 1966 Birth Cohort was followed until age 31, when, in a cross-sectional setting (n = 5269), in males, elevated hs-CRP levels (>/=1.0 mg/L) increased the probability for severe current and recurrent depressive episodes 70% and 210%, respectively. Correspondingly, an hs-CRP level of >3.0 mg/L increased the probability for recurrent depression up to 310%. In females, no statistically significant associations were found. The Association Between C-Reactive Protein Levels and Depression: Results from the Northern Finland 1966 Birth Cohort Study. Liukkonen T, et al. Savonlinna, Finland. Biol Psychiatry 2006 Apr 7.

Insomnia Predicts Later Depression: Eight relevant epidemiological studies were identified. Almost unambiguously primary insomnia at baseline significantly predicted an increased depression risk at follow-up 1-3 years later. Univ Freiburg, Primary insomnia: a risk factor to develop depression? Riemann D, Voderholzer U. J Affect Disord. 2003 Sep;76(1-3):255-9

Insomniac Elderly More Likely to Become Depressed: In a 1-year follow-up study of 147 men and women over the age of 60 with no history of mental illness, 34 had persistent insomnia, 47 less persistent "indeterminate insomnia," while 66 had no sleep troubles. During the year, 12 developed depression: 6 with persistent insomnia, 4 had indeterminate insomnia and 2 no trouble sleeping. Elderly patients with persistent insomnia were six times more likely to experience serious new-onset depression than individuals who sleep easily. Ten of the 12 depressed patients were women, and all the patients who became depressed while suffering from a persistent form of insomnia were female. Perlis said its unclear why elderly women might be at especially high risk for the insomnia-depression connection. Perlis, M, et al. University of Rochester, J Behavioral Sleep Medicine late 2005. Another study by Perlis of 1,221 elderly treated for depression, those with insomnia were 12 times more likely to still be depressed 6 months later and 10 times more likely to be depressed 1 year later. Ed: This may be a lack of serotonin, which is converted into melatonin to aid sleep. A lack of melatonin causes insomnia, while depression is often caused by a lack of serotonin effect. 5-HTP, a serotonin precursor, has been used for depression. I would hypothesize that it is better for depression with insomnia than depression without insomnia and that it might prevent depression in elderly with insomnia. 

Left Subgenual Cingulate Involved: Left subgenual cingulate volume reductions (19% decr) are present in young women with adolescent onset MD (Major Depression). Biol Psychiatry 2002 Feb 15;51(4):342-4.

Low Birth Weight Girls More Depressed: In a study of more than 1,400 children, aged nine to 16, girls born weighing less than 5.5 pounds, 5.7% of the girls in the study, had a 38% risk of depression at least once between the ages of 13 and 16 vs. 8.4% of those born at a normal weight. On average, 23.5% of teenage girls with a low birth weight were depressed each year, compared with 3.4% of those born at a normal weight. Regardless of their birth weight, no more than 4.9% of the boys experienced depression. Low birth weight was not linked to an increased risk of any other psychiatric condition, including anxiety disorders, in either boys or girls. Previous research has linked low birth weight to an increased risk of attention deficit disorder, as well as physical conditions such as cardiovascular disease, and diabetes. Duke University. Arch Gen Psychiatry 3/07.

Low Birth Weight: A 45-year follow-up study of the 5572 children in Aberdeen, Scotland found that those who were born weighing under 5.5 pounds were 50% more likely to suffer from anxiety and depression in adulthood.  This was true regardless of social class. Nicola Wiles et al. London School of Hygiene, Br J Psychiatry 7/1/05. Low birth weight has also been linked to cancer and diabetes.

Medically CoMorbid Patients Respond as Well: Open Harvard study of 92 treatment resistant patients given nortriptyline found that those with Axis III medical conditions responded just as well. Axis III disorders in treatment-resistant major depressive disorder. Papakostas GI, Petersen T, Iosifescu DV, Roffi PA, Alpert JE, Rosenbaum JF, Fava M, Nierenberg A Psychiatry Res. 2003 May 30;118(2):183-8

Melatonin May be Involved in Depression: Baseline melatonin was significantly lower in depressed patients than controls (P=0.004). Melatonin following atenolol administration was strongly reduced in both groups (P < 0.0001). This reduction depends on whether the subject is a high or low (cutoff: 0.25 nmol/l) baseline melatonin excretor (P=0.025) and on whether he is depressed being a low excretor (P=0.048). A negative correlation (P=0.007) was found between melatonin decrease after atenolol and the Montgomery-Asberg Depression Rating Scale score. Acta Psyc Scan 02;106:440

Monoamine Osidase A Lowers Serotonin and Norepinepherine: In a study of 17 healthy and 17 depressed individuals with major depressive disorder, medication free for at least 5 months, the enzyme monoamine oxidase A DV(S) was highly significantly elevated in every brain region assessed (P = .001 to 3x10(-7)) by an average of 34% during major depression. Elevated MAO-A density is the primary monoamine-lowering process during major depression. Elevated monoamine oxidase a levels in the brain: an explanation for the monoamine imbalance of major depression. Meyer JH, et al. University of Toronto. Arch Gen Psychiatry 2006 Nov;63(11):1209-16.

Multiple Sclerosis Patients More Depression: A 115,000 Canadian adult survey found adults with MS had a 26% prevalence of major depression in a one year period of time, a 130% increase (OR = 2.3) over the norm. Major depression in multiple sclerosis: A population-based perspective. Patten SB, Beck CA, Williams JV, Barbui C, Metz LM. Neurology. 2003 Dec 9;61(11):1524-7

Murder-Suiciders Rarely in Treatment: Only 3 of 127 merder-suiciders were on anti-depressants in New York City from 1990-1998. Tardiff AJP 7/02

Obesity is Depressing; Weight Loss Helps: 487 subjects, the mean preoperative BDI score was 17.7. Higher scores, indicating increased symptoms of depression, were found in younger subjects, women, and those with poorer body image. These factors had independent effects. We found no association between BDI and waist circumference or insulin concentrations. High BDI scores correlated with poorer physical and mental quality-of-life measures. Weight loss was associated with a significant and sustained fall in BDI scores, with a mean score of 7.8 at 1 year and 9.6 at 4 years after surgery. Greater falls in BDI score at 1 year were seen in women, younger subjects, and those with greater excess weight loss (combined r2 = 0.10; P<.001). Fall in BDI score correlated with improvement in appearance evaluation (r = -0.31; P<.001). Depression in association with severe obesity: changes with weight loss. Dixon JB, Dixon ME, O'Brien PE. Arch Intern Med. 2003 Sep 22;163(17):2058-65

Orbital Frontal Cortex Reduced: Patients with depression had a statistically significant 32% smaller medial orbitofrontal (gyrus rectus) cortical volume, without smaller volumes of other frontal regions including anterior cingulate Brodmann's area 24 (subgenual gyrus), anterior cingulate Brodmann's area 32, subcallosal gyrus (Brodmann's area 25), or whole brain volume. Biol Psychiatry 2002 Feb 15;51(4):273-9

P11 Protein Reduces Depression: The brain protein p11 makes cells more receptive to serotonin. As it rises, depression lifts in people and in mice bred susceptible to depression. It interacts with serotonin 1B receptor, which is involved in depression, by moving the ceptor to the membrane to make it functional. Mice without the p11 gene were depressed, while those with too much p11 were hyperactive. Human autopsies show lowest p11 in those depressed just before death. Philip Cowen, University of Oxford. New Sci 1/14/06.

Parkinson’s Disease Depression Common and Vastly Under-treated: 100 Parkinson’s patients tested at a Parkinson’s Disorder Center. One third (34%) of subjects met criteria for a depressive disorder, and two thirds (65%) of them were not currently receiving antidepressant treatment. Approximately one quarter (23%) of subjects were taking an antidepressant, but almost half (47%) of them still met criteria for a depressive disorder. Few antidepressant users with persistent depression had received either antidepressant treatment at dosages within the highest recommended range (11%) or more than 1 antidepressant trial (33%). Phila VA. Recognition and treatment of depression in Parkinson's disease. Weintraub D, Moberg PJ, Duda JE, Katz IR, Stern MB. J Geriatr Psychiatry Neurol. 2003 Sep;16(3):178-83

Post-Partum Depression Linked to Infant Insecurity: 136 women assessed before and at 4 wk and 4 mo post-partum. 20% were depressed at one of the two measurements. Children of those mothers showed decreased secure attachments at 12 months (33% vs. 60%). Cassidy, Toronto, APA 5/30/98 Toronto

Rapid-Cycling Not Due to Tricyclics: 345 bipolar I or bipolar II pts 13.7 years follow-up in National Institute of Mental Health Collaborative Depression Study, 25.8% had rapid cycling during 1 or more years. They were significantly more likely to have had an illness onset before 17 years of age and were more likely to make serious suicide attempts. In 4 of 5 cases, rapid cycling ended within 2 years of its onset. Resolutions were not associated with decreases in tricyclic antidepressant use. Throughout follow-up, patients prone to rapid cycling experienced more depressive morbidity than other bipolar patients, particularly when lithium carbonate was being used without tricyclic antidepressants. The use of these antidepressants was not more likely in the weeks preceding shifts from depression to mania or hypomania. The long-term course of rapid-cycling bipolar disorder. NIMH. Coryell W, et al. Arch Gen Psychiatry. 2003 Sep;60(9):914-20

Recurrence Risk: MDD is often a recurrent illness, and the risk of recurrence increases with each episode. A patient who has experienced 1 prior depressive episode has a 50% chance of experiencing another. After the second episode, the probability of a third episode is 70%. With a history of 3 or more prior episodes, the probability of a subsequent episode rises to 90%. US Agency for Health Care Policy and Research. Depression in Primary Care: Volume 2. Treatment of Major Depression (Clinical Practice Guideline Number 5) (AHCPR Publication No. 93-0551). April 1993

Serotonin Low Underlies Pessimism: Three different MRI studies 1) using d-fenfluramine to stimulate serotonin release decreased pessimism in normals. 2) PET scans compared the serotonin receptor binding potential finding in MDD pts with pessimism an abnormally large number of serotonin receptors in the brain, and especially in the prefrontal cortex area, underlies the pessimism accompanying a major depression. Jeff Meyers, U Toronto, Am J Psych 38:34, 01/03. 

Sleep Apnea May Increase Psychiatric Illness: Using the Veterans Health Administration databases for more than 4 million veterans 118,105 were identified as having sleep apnea (3%). Mean age at diagnosis was 58. Psychiatric comorbid diagnoses in the sleep apnea group included depression (22%), anxiety (17%), posttraumatic stress disorder (12%), psychosis (5%), and bipolar disorders (3%). Compared with patients not diagnosed with sleep apnea, a significantly greater prevalence (P < .0001) was found for mood disorders, anxiety, posttraumatic stress disorder, psychosis, and dementia. Association of psychiatric disorders and sleep apnea in a large cohort. Sharafknaneh A, et al. Baylor College of Medicine. . Sleep 2005 Nov 1;28(11):1405-11.

Strokes More Common in Depressed: A 29 year follow-up of 6,676 healthy Alameda adults found after controlling for smoking, hypertension, diabetes, alcohol, weight, etc., that depression still strongly linked to more stroke deaths with RR 1.54. Everson, Arch Int Med ’98;158:1133

Strokes-Silent Ones More Common in Depressed: In those over 50, 3660 tested for depression. MRIs found depressed had many small lesions in basal ganglia and frontal areas. Range Krishnan of Duke says arteriosclerotic or vascular depression accounts for 30-40% depression in over 65s. Stroke, 2000.

Substance Abuse with Depression More Impaired and More Suicidal: If a study of 1484 adults with a major depressive disorder, 28% reported a current substance abuse disorder. These were more likely to be men (P < .0001), to be either divorced or never married (P = .018), to have a younger age of onset of depression (P = .014), and to have a higher rate of previous suicide attempts (P = .014). They also reported greater functional impairment due to their illness (P = .0111). The presence of SUD symptoms did not alter the overall depressive symptom pattern of presentation, except that the dual-diagnosed patients had higher levels of hypersomnia (P = .006), anxious mood (P = .047), and suicidal ideation (P = .036). Substance use disorder comorbidity in major depressive disorder: an exploratory analysis of the Sequenced Treatment Alternatives to Relieve Depression cohort. Davis LL, Rush JA, et al. VA Medical Center, Tuscaloosa, AL. Compr Psychiatry. 2005 Mar-Apr;46(2):81-9.

Suicide Attempts Common: Depression, Smoking, Drugs Factors: Data from 3357 men and 4004 women ages 17-39 interviewed as a part of the Third National Health and Nutrition Examination Survey, 1988-1994 found the prevalence of lifetime attempted suicides was 7.6% in women and 3.7% in men. In men, low income and smoking were associated with attempted suicide, while attempted suicide in women was associated with poor self-evaluated health, low educational attainment, and drug use. A history of medical and psychiatric illnesses was associated with attempted suicide in both genders, for cancer/pulmonary disease, OR=2.9 in men and 1.9 in women; for major depressive disorder, OR=9.9 in men and 5.0 in women. Gender differences in risk factors for attempted suicide among young adults: findings from the Third National Health and Nutrition Examination Survey. Zhang J, McKeown RE, et al. University of South Carolina. Ann Epidemiol. 2005 Feb;15(2):167-74

Suicide Risk Only 2-4%: Review of 100 studies of depression and suicide found 2% out-patient depression goes on to suicide and 4% of in-patient depression does. In general population, rate is 1%. Mayo Clinic. Amer J Psychiatry 12/00

Suicide Decreased After Sept. 11th, 2001: The tragic events of 11 September 2001 appear to have had a brief but significant inverse effect on suicide, but not murder in England. The finding of this study supports Durkheim's theory that periods of external threat create group integration within society and lower the suicide rate through the impact on social cohesion. Effect of 11 September 2001 on suicide and homicide in England and Wales. Salib E. Br J Psychiatry. 2003 Sep;183:207-12

Suicide Attempters in Follow-up: A UK mortality follow-up study of 11 583 patients who presented to hospital after deliberate self-harm (DSH). 300 patients had died by suicide or probable suicide. The risk in the first year of follow-up was 0.7%, which was 66 times the annual risk of suicide in the general population. The risk after 5 years was 1.7%, at 10 years 2.4% and at 15 years 3.0%. The risk was far higher (180%) in men than in women.  Suicide following deliberate self-harm: long-term follow-up of patients who presented to a general hospital. Hawton K, Zahl D, Weatherall R. Br J Psychiatry. 2003 Jun;182:537-42

Summer Depression Much More in Chinese Report: Two studies in China find med students and college students report more depr diff in summer than winter (38% vs. 20%). Ling Han, Montreal (study in Jining, China), APA 5/99

Taliban Policies Increased Female Depression: In household residences in two regions in Afghanistan (one Taliban controlled and the other not under the Taliban) and a refugee camp and repatriation center in Pakistan, structured interviews were conducted among a random sample of women and men exposed to Taliban policy and women living in a non-Taliban controlled area (724 Afghan women and 553 male relatives). RESULTS: Major depression was far more prevalent among women exposed to Taliban policies (73%-78%) than among women living in a non-Taliban controlled area (28%). Sixty-five percent of women living in a Taliban-controlled area and 73% of women in Pakistan exposed to Taliban policies expressed suicidal ideation at the time of the study, compared with 18% of those in a non-Taliban controlled area. More than 90% of both women and men expressed support for equal work and educational opportunities, free expression, protection of women's rights, participation of women in government, and the inclusion of women's human rights concerns in peace talks. A majority of both women and men believed that guaranteeing civil and political rights (69%) and meeting basic needs (90%). A population-based assessment of women's mental health and attitudes toward women's human rights in Afghanistan. Amowitz LL, Heisler M, Iacopino V. Physicians for Human Rights, Boston, J Womens Health (Larchmt). 2003 Jul-Aug;12(6):577-87

Thyroid Difficulties No More in Young Depressed Women: Data of NHANES-3 (Natl health and nutrition exam survey-3rd) of 4047 females 17-39 found 47% history of depression. Those more depressed were likely to have had chest pain (34% vs. 19%), hypertension (15% vs. 10%) and diabetes (3.6% vs. 2.3%) but not lupus or thyroid disease. A Gupta, U Maryland APA 5/99.

Traditional Mutual and Intergenerional Aid Linked to Less Depression: As the traditional culture declines so do these familiar roles, supports, and ways of coping. In a study of 1502 Chinese elders living in the People's Republic of China with a nine-item measure of traditional mutual aid and intergenerational exchange, there was a significant negative relationship between tradition and depression which suggests that adherence to tradition may have protective benefits. Relationship between adherence to tradition and depression in Chinese elders in China. Mjelde-Mossey LA, et al. Ohio State University, and University of Hong Kong. Aging Ment Health 2006 Jan;10(1):19-26.

Vegetarians Less Depressed?: More anxiety and depression were reported in the non-vegetarian groups in comparison with the vegetarian groups. However, there were only 80 people in the study. Puerto Rico. Bol Asoc Med P R 1998 Apr-Jun;90(4-6):58-68

Young Mother's Offspring More Suicide and Drugs: In a cohort study based on Swedish national registers of 292,129 children born to primiparas women, youths born of teenage mothers had a 90% higher risk for suicide death [RR 1.9, 95% CI 1.3-2.7] and 100% more hospital admissions because of suicide attempt (RR 2.0, 95% CI 1.7-2.3) and substance abuse (alcohol: 60%; illicit drug: 120%) after adjustments for major sociodemographic confounders, compared with children of mothers aged 25-29 years. Offspring of older parents (>34 years) had an 80% higher risk for schizophrenia. Psychiatric morbidity is related to parental age: a national cohort study. Ekeus C, et al. Karolinska Institute, Sweden. Psychol Med 2006 Feb;36(2):269-76. Ed: While this study attempts to control for founders, there is no way a first time teen mother can be matched to a first time mother in her late 20s, even from the same social class.  This is almost certainly a social phenomenon, not a biological one. In contrast, the older parents-schizophrenia connection is the opposite.