Click "Up" to get to the primary page for Bipolar Disorder.  Below are non-treatment, non-genetic studies.

Anger Attacks More Common in Bipolar than Unipolar Depression: Sudden episodes of intense anger with autonomic arousal occurred in 26% of 50 depressed out-patients with major depressive disorders, but in 62% of bipolar patients in depressed phases. The presence of anger attacks emerged as a significant predictor of bipolarity. The prevalence and clinical correlates of anger attacks during depressive episodes in bipolar disorder. Perlis RH, Smoller JW, et al. Massachusetts General. J Affect Disord. 2004 Apr;79(1-3):291-5

Autoimmunity in Bipolars found Increased: There is an increased prevalence of thyroperoxidase antibodies (TPOA) in patients with bipolar disorder as well as other organ-specific autoantibodies: H/K adenosine triphosphatase (ATPA), and glutamic acid decarboxylase-65 (GAD65A)(11.7 vs. 6.1% and 11.3 vs. 2.6% respectively; p <.05) in 239 bipolars vs. 220 controls. No increase was found in schizophrenia. Bipolar disorder is associated with organ-specific autoimmunity to the antigens TPO, H/K ATPase, and GAD65. A high prevalence of organ-specific autoimmunity in patients with bipolar disorder. Padmos RC, Bekris L, et al. Erasmus Medical Centre, Rotterdam, The Netherlands. Biol Psychiatry. 2004 Oct 1;56(7):476-82. Ed: Since vegan diets and fish oil help a number of other autoimmune diseases, one wonders if bipolar disorder is similar.

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: Head Injury Cases 55% Higher Risk of Bipolar Disease: A large Danish study by Aarhus University examining psychiatric hospitalizations of 10,242 bipolars and for 102,420 controls.  Bipolars had a slightly increased likelihood of head injury in the five years preceding their first admissions. Researchers concluded head injury was a cause of a small percentage of bipolar cases. Head injury as a risk factor for bipolar affective disorder. Mortensen PB, Mors O, et al. J Affect Disord. 2003 Sep;76(1-3):79-83.

Brain: Deep White Matter Hyperdensities More Common in Bipolars: In a study of 43 bipolar patients and 39 healthy adults, patients with bipolar disorder had greater prevalence of white matter hyperdensity (WMH) abnormalities (Bipolar, grade 1 = 11.6%, grade 2 = 9.3%, grade 3 = 7.0%; Comparison, grade 1 = 5.1%, grade 2 = 2.6%, grade 3 = 0%). This difference is mainly due to the differences in deep WMH (Bipolar, grade 1 = 14.0%, grade 2 = 14.0%; Comparison, grade 1 = 7.7%, grade 2 = 0%). White matter hyperintensities in subjects with bipolar disorder. Ahn KH, Lyoo IK, et al. Harvard-McLean. Psychiatry Clin Neurosci. 2004 Oct;58(5):516-21.

Callosal Areas of Brain Smaller in Bipolars: An MRI study, after controlling for various factors and comparing 27 bipolar patients to the same number of controls found small callosal areas in the bipolars. Smaller callosal areas may lead to altered inter-hemispheric communication and be involved in the pathophysiology and cognitive impairment found in bipolar disorder. Univ. Pittsburgh. Magnetic resonance imaging study of corpus callosum abnormalities in patients with bipolar disorder. Brambilla P, Nicoletti MA, et al. Biol Psychiatry. 2003 Dec 1;54(11):1294-7

Cognition: Very Small Study Found Half of Elderly Bipolars with Cognitive Difficulties: 18 euthymic elderly older than 59 with a bipolar disorder I or II were compared to 45 matching elderly without mood disorders. 50% of the bipolar individuals scored one or more standard deviations below the mean of the comparison subjects on the MMSE or the Mattis Dementia Rating Scale. On the Executive Interview, three subjects (17%) scored between one and two standard deviations below the mean of the comparison subjects. Cognitive functioning in late-life bipolar disorder. Gildengers AG, Butters MA, et al. University of Pittsburgh. Am J Psychiatry. 2004 Apr;161(4):736-8

Cycloid Psychosis a Separate Illness: All (431) living and traceable adult first-degree relatives of 45 cycloid psychotic, 32 manic-depressive and 27 control adults were personally examined. Relatives of cycloid psychotic patients showed a significantly lower morbidity risk for endogenous psychoses in general and manic-depressive illness compared to relatives of patients with manic-depressive illness. The familial morbidity risk for cycloid psychoses was low and did not differ significantly in both proband groups. Relatives of cycloid psychotic patients however did not differ significantly from relatives of controls regarding familial morbidity. Cycloid psychoses are not part of a bipolar affective spectrum: results of a controlled family study. Pfuhlmann B, Jabs B, et al. University of Wuerzburg, Germany. J Affect Disord. 2004 Nov 15;83(1):11-9.

Dementia Risk Increased in Bipolars: In a case register study including all hospital admissions with primary affective disorder in Denmark during 1970-99, 18,726 patients with depressive disorder and 4248 patients with bipolar disorder were included in the study. The rate of dementia increased on average 13% with every depressive episode leading to admission and 6% with every manic episode, when adjusted for differences in age and sex. Does the risk of developing dementia increase with the number of episodes in patients with depressive disorder and in patients with bipolar disorder? Kessing LV, Andersen PK. University Hospital of Copenhagen. J Neurol Neurosurg Psychiatry. 2004 Dec;75(12):1662-6.

Herpes: Cognitive Dysfunction Bipolars Have Antibodies to Herpes Type I: An association has been documented between reduced cognitive functioning and the prevalence of antibodies to herpes simplex virus type 1 in individuals with schizophrenia. In a study of 117 bipolar patients and in 100 without a history of psychiatric disorder, serologic evidence of infection with herpes simplex virus type 1 was an independent predictor of decreased cognitive functioning in the individuals with bipolar disorder (F = 20.5, p <.0001), primarily immediate verbal memory (F = 12.07, p <.001). There was no significant association between cognitive functioning and the other human herpesviruses. No association between antibodies to herpesviruses and cognitive functioning was found in the control individuals without a history of psychiatric disorder. Infection with herpes simplex virus type 1 is associated with cognitive deficits in bipolar disorder. Dickerson FB, Boronow JJ, et al, Baltimore. Biol Psychiatry. 2004 Mar 15;55(6):588-93

Hippocampal Mitochondria Not Working Well in Bipolars: To determine the expression of 12558 nuclear genes in the human hippocampus in healthy control subjects and those with bipolar disorder or schizophrenia gene arrays were used to study messenger RNA expression in 10 healthy control subjects, 9 subjects with bipolar disorder, and 8 subjects with schizophrenia. The expression of nuclear messenger RNA coding for mitochondrial proteins was significantly decreased in the hippocampus in  bipolar disorder but not in schizophrenia. There was a pronounced and extensive decrease in the expression of genes regulating oxidative phosphorylation and the adenosine triphosphate-dependent process of proteasome degradation involved in mitochondrial energy metabolism. Molecular evidence for mitochondrial dysfunction in bipolar disorder. Konradi C, Eaton M, et al. Harvard. Arch Gen Psychiatry. 2004 Mar;61(3):300-8

Marijuana Abuse Rampant in Pittsburgh Study: In a small DB PC study testing valproate in 52 bipolar alcoholics, researchers found that 48% reported marijuana abuse. These marijuana abusers were younger, had fewer years of education, and had significantly higher additional psychiatric comorbidity. They also had more severe alcohol and other drug use and were significantly more likely to present in the manic phase. The placebo-treated marijuana abuse group had the worst alcohol use outcome. Patient characteristics and treatment implications of marijuana abuse among bipolar alcoholics: Results from a double blind, placebo-controlled study. Salloum IM, et al. University of Pittsburgh. Addict Behav. 2005 Aug 10.

Mixed Depressive-Manic Features May Predict a Manic Switch in Bipolar Depression: In a study of the medical records of 158 bipolar I depressives, the number of mixed depressive symptoms (flight of ideas, racing thoughts, logorrhea, aggression, excessive social contact, increased drive, irritability, and distractibility) at admission was associated with a higher risk for, and the acceleration of, a manic switch during inpatient treatment. Mixed depressive features predict maniform switch during treatment of depression in bipolar I disorder. Bottlender R, et al. Ludwig-Maximilians University, Munich, Germany. J Affect Disord. 2004 Feb;78(2):149-52.

Menstrual Irregularity as Teens More Common In Bipolars: The prevalence of early-onset (within the first 5 postmenarchal years) menstrual cycle dysfunction (menstrual cycle length unpredictable within 10 days or menstrual cycle length<25 days or >35 days) occurring before onset of psychiatric illness was clearly higher in 101/295 women with bipolar disorder (34.2%), 60/245 women with depression (24.5%), and 134/619 healthy controls (21.7%)(p<.0001). Menstrual dysfunction prior to onset of psychiatric illness is reported more commonly by women with bipolar disorder than by women with unipolar depression and healthy controls. Joffe H, et al. MGH- Harvard. . J Clin Psychiatry 2006 Feb;67(2):297-304.

Menstrual Problems Common in Bipolar Women, Especially Oligomenorrhea: In a study of 80 bipolar women not on birth control pills, 65% reported current menstrual abnormalities, and 50% reported one or more menstrual abnormalities that preceded the diagnosis of bipolar disorder. Of the 15 developing menstrual abnormalities since treatment for bipolar disorder, 14 were on valproate (p = 0.04). Of the 15, 12 reported changes in menstrual flow (heavy or prolonged bleeding) and five (33%) reported changes in cycle frequency. No significant differences were observed between women receiving or not receiving valproate in mean levels of free or total serum testosterone levels. Three of the 50 women (6%) taking VPA, and 0% of the 22 taking other antimanic medications, met criteria for PCOS (p = 0.20). Other reproductive and metabolic values outside the normal range across treatment groups included elevated 17 alpha-OH progesterone levels, luteinizing hormone: follicle-stimulating hormone ratios, homeostatic model assessment (HOMA) values, and low estrogen and dehydroepiandrosterone sulfate (DHEAS) levels. Preexisting menstrual abnormalities predicted higher levels of 17 alpha-OH progesterone, free testosterone, and estrone as well as development of new menstrual abnormalities. Body mass index (BMI) was significantly positively correlated with free testosterone levels and insulin resistance (HOMA) across all subjects, regardless of medication used. Reproductive function and risk for PCOS in women treated for bipolar disorder. Rasgon NL, Altshuler LL, et al. Stanford A. Bipolar Disord 2005: 7: 246-259.  The same authors report following 25 bipolar women for 2 years with 42% suffering oligomenorrhea unaffected by medication usage. J Affect Disord. 2005 Sep 17

Metabolic Disorder, Obesity Very Common in Pennsylvania Bipolars; Attempt Suicide More Often: In a study of 171 patients recruited in the Bipolar Disorder Center for Pennsylvanians, 30% had metabolic syndrome, 49% abdominal obesity, 48% hypertriglyceridemia or were on a cholesterol-lowering medication, 23% low high-density lipoprotein cholesterol, 39% hypertension and 8% diabetes. Patients with the metabolic syndrome and patients with obesity  were more likely (p = 0.05 and p = 0.004, respectively) to report a lifetime history of suicide attempt/s. The prevalence of the metabolic syndrome in patients with bipolar disorder is alarmingly high. The authors strongly support the development and testing of interventions specifically designed for preventing and treating the metabolic syndrome and its components in patients with bipolar disorder. Metabolic syndrome in bipolar disorder: findings from the Bipolar Disorder Center for Pennsylvanians. Fagiolini A, et al. University of Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic, Pittsburgh and Dubois Regional Medical Center. Bipolar Disord. 2005 Oct;7(5):424-30.

Schizoaffective Disorder: Retrospective Study Suggests Schizoaffective Disorder Often an Extension of Bipolar: In a retrospective study of at least a 5-year period for 61 schizoaffective, 57 bipolar I, and 55 schizophrenic outpatients, the schizoaffective disorder patients had a profile similar to the bipolar I patients but were significantly different from schizophrenic patients in educational level, marital status, occupation, drug and alcohol abuse episodes, presence of depressive, mixed and maniac episodes, family history of bipolar I and mood disorders, and use of medications. Only the age of onset, suicide attempts, and family history of suicide are not significantly different among the groups. The schizophrenic patients used antipsychotics for more days and the schizoaffective and bipolar I used more antidepressants and mood stabilizers. 37 (60.6%) schizoaffective patients had their diagnosis changed to bipolar disorder by their physician in different periods during the period studied. Demographic and clinical features of schizoaffective (schizobipolar) disorder-A 5-year retrospective study. Support for a bipolar spectrum disorder. Nardi AE, et al. Federal University of Rio de Janeiro. J Affect Disord. 2005 Sep 29

Smoking High in Bipolars, Schizophrenics: A study of 2774 psychiatric outpatients found that 61% smoked daily and 18% heavily. Smoking was especially related to diagnoses of bipolar disorder, schizoaffective disorder, and schizophrenia an association that was most pronounced among the most severe, even after controlling for other substance use. Cessation programs are needed. Univ. Syracuse. Smoking among psychiatric outpatients: relationship to substance use, diagnosis, and illness severity. Vanable PA, Carey MP, Carey KB, Maisto SA. Psychol Addict Behav. 2003 Dec;17(4):259-65

Visuospatial Testing Poor Performance Predicts High Risk of Bipolar Disorder: Results on verbal, arithmetic, and visuospatial reasoning tests were obtained for 195,019 apparently healthy 19-20 year old male draftees into the Finnish Defense Forces. Follow-up 7.1 years later identified those developing bipolar disorder (N=100), schizophrenia (N=621), or other psychoses (N=527). There was a 34 times higher risk of developing bipolar disorder between the lowest and highest of nine categories of performance on visuospatial tested (OR=34.65) for bipolar disorder, 13.76 times higher for schizophrenia, and 4.28 times higher for other psychoses. In contrast, the higher the score for arithmetic reasoning, the greater the risk of bipolar disorder; a high score was associated with a more than 12-fold greater risk. Verbal test performance was not associated with higher risk for psychiatric disorder. Premorbid intellectual functioning in bipolar disorder and schizophrenia: results from a cohort study of male conscripts. Tiihonen J, et al. University of Kuopio, Finland. . Am J Psychiatry. 2005 Oct;162(10):1904-10. Ed: Finland must not diagnose Bipolar Disorder as often as American psychiatrists, since 100 out of 195,000 is many times smaller than what would be diagnosed in the U.S. where almost anyone with depression and irritability is called Bipolar.

Thomas E. Radecki, M.D., J.D.

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