[Click here to find out more about
bipolar disorder genetic factors.]
Post RM, Leverich
GS, Xing G, Weiss RB.
Developmental vulnerabilities to the onset
and course of bipolar disorder.
Dev Psychopathol 2001 Summer;13(3):581-98
"Different types of psychosocial stressors have long been recognized as potential
precipitants of both unipolar and bipolar affective episodes and the causative
agents in posttraumatic stress disorder (PTSD). New preclinical data have revealed
some of the neurobiological mechanisms that could convey the long-term behavioral
and biochemical consequences of early stressors. Depending on the timing, quality,
quantity, and degree of repetition, maternal deprivation stress in the neonatal
rodent can be associated with lifelong anxiety-like behaviors, increases in stress
hormones and peptides. and proneness to drug and alcohol administration, in association
with acute changes in the rate of neurogenesis and apoptosis (preprogrammed cell
death) and decrements in neurotrophic factors and signal transduction enzymes
necessary for learning and memory. Patients with bipolar illness who have a history
of early extreme adversity (physical or sexual abuse in childhood or adolescence),
compared with those without, show an earlier onset of illness, faster cycling
frequencies, increased suicidality, more Axis I and Axis II comorbidities (including
alcohol and substance abuse), and more time ill in more than 2 years of prospective
follow-up. These findings are subject to a variety of interpretations, but to
the extent that the more severe course of bipolar illness characteristics are
directly and causally related to these early stressful experiences, early recognition
and treatment of high-risk children could be crucial in helping to prevent or
ameliorate the long-term adverse consequences of these stressors." [Abstract]
GS, McElroy SL, Suppes T, Keck PE Jr, Denicoff KD, Nolen WA, Altshuler LL, Rush
AJ, Kupka R, Frye MA, Autio KA, Post RM.
Early physical and sexual
abuse associated with an adverse course of bipolar illness.
Biol Psychiatry 2002 Feb 15;51(4):288-97
"BACKGROUND: There is growing
awareness of the association between physical and sexual abuse and subsequent
development of psychopathology, but little is known, however, about their relationship
to the longitudinal course of bipolar disorder. METHODS: We evaluated 631 outpatients
with bipolar I or II disorder for general demographics, a history of physical
or sexual abuse as a child or adolescent, course of illness variables, and prior
suicide attempts, as well as SCID-derived Axis I and patient endorsed Axis II
comorbidity. RESULTS: Those who endorsed a history of child or adolescent physical
or sexual abuse, compared with those who did not, had a history of an earlier
onset of bipolar illness, an increased number of Axis I, II, and III comorbid
disorders, including drug and alcohol abuse, faster cycling frequencies, a higher
rate of suicide attempts, and more psychosocial stressors occurring before the
first and most recent affective episode. The retrospectively reported associations
of early abuse with a more severe course of illness were validated prospectively.
CONCLUSIONS: Greater appreciation of the association of early traumatic experiences
and an adverse course of bipolar illness should lead to preventive and early intervention
approaches that may lessen the associated risk of a poor outcome." [Abstract]
P, Dias A, Todd G, Bowen-Jones K, Reilly B, Bentall RP.
trauma and hallucinations in bipolar affective disorder: preliminary investigation.
J Psychiatry. 2003 Jun;182:543-7.
"BACKGROUND: Strong evidence exists
for an association between childhood trauma, particularly childhood sexual abuse,
and hallucinations in schizophrenia. Hallucinations are also well-documented symptoms
in people with bipolar affective disorder. AIMS: To investigate the relationship
between childhood sexual abuse and other childhood traumas and hallucinations
in people with bipolar affective disorder. METHOD: A sample of 96 participants
was drawn from the Medical Research Council multi-centre trial of cognitive-behavioural
therapy for bipolar affective disorder. The trial therapists recorded spontaneous
reports of childhood sexual abuse made during the course of therapy. Symptom data
were collected by trained research assistants masked to the hypothesis. RESULTS:
A significant association was found between those reporting general trauma (n=38)
and auditory hallucinations. A highly significant association was found between
those reporting childhood sexual abuse (n=15) and auditory hallucinations. CONCLUSIONS:
The relationship between childhood sexual abuse and hallucinations in bipolar
disorder warrants further investigation." [Abstract]
SL, Fan AP.
Association of prenatal and perinatal complications
with subsequent bipolar disorder and schizophrenia.
Res 1999 Sep 29;39(2):113-9; discussion 160-1
"This paper presents an
overview of the recent literature on the association between prenatal and perinatal
complications (PPCs) and schizophrenia, then systematically reviews papers published
later than 1965 examining the association of PPCs and bipolar disorder. Three
of the four studies comparing bipolar cases with normal controls indicated a positive
association of PPCs with the development of bipolar disorder in adult life; the
four odds ratios ranged from 1.0 to 12.0. The proportion of PPCs among the bipolar
samples without comparison subjects ranged from 3.8% to 50.0%. Issues of study
design, measurement and severity of exposure, and outcome are addressed. This
review suggests that further investigation of genetic interactions, gender differences,
and the specificity of effects in the association between PPCs and mental disorders
other than schizophrenia is warranted." [Abstract]
M, Reichart CG, Hillegers MH, Van Os J, Verhulst FC, Nolen WA, Ormel J.
of birth weight and genetic liability on psychopathology in children of bipolar
J Am Acad Child Adolesc Psychiatry. 2003 Sep;42(9):1116-21.
To test different models for ways in which birth weight and familial loading influence
the risk for psychopathology in bipolar offspring. METHOD: DSM-IV diagnoses of
140 bipolar offspring (12-21 years of age) were assessed with the K-SADS-PL. Parents
were interviewed using the Family History-Research Diagnostic Criteria to determine
familial loading of mood and substance use disorders. Parents reported the birth
weight of their offspring. Age- and sex-adjusted hazard ratios were calculated.
RESULTS: Low birth weight was associated with mood and non-mood disorders in bipolar
offspring (hazard ratio = 0.6, confidence interval = 0.4-0.8), even after controlling
for familial loading of unipolar disorder, bipolar disorder, or substance use
disorder. There were no significant interactions between birth weight and familial
loading of unipolar disorder, familial loading of bipolar disorder, and familial
loading of substance use disorder. CONCLUSIONS: Birth weight is associated with
mood as well as non-mood disorders. This association is independent from the association
of familial loading of mood and substance use disorder with mood- and non-mood
disorders in bipolar offspring." [Abstract]
Brown AS, van Os J, Driessens
C, Hoek HW, Susser ES.
Further evidence of relation between prenatal
famine and major affective disorder.
Am J Psychiatry 2000
"OBJECTIVE: In a previous study, the authors demonstrated
an association between prenatal famine in middle to late gestation and major affective
disorders requiring hospitalization. In this study, they sought to examine the
association by using newly identified cases from the Dutch birth cohort used previously
to examine the gender specificity of the association and to assess whether this
relation is present for both unipolar and bipolar affective disorders. METHOD:
The authors compared the risk of major affective disorder requiring hospitalization
in birth cohorts who were and were not exposed, in each trimester of gestation,
to famine during the Dutch Hunger Winter of 1944-1945. These cases of major affective
disorder requiring hospitalization were newly ascertained from a national psychiatric
registry. A larger data set from this registry was used for analysis by gender
and diagnostic subtype. RESULTS: For the newly ascertained cases, the risk of
developing major affective disorder requiring hospitalization was increased for
subjects with exposure to famine in the second trimester and was increased significantly
for subjects with exposure in the third trimester, relative to unexposed subjects.
For the cases from the entire period of ascertainment, the risk of developing
affective disorder was significantly increased for those exposed to famine during
the second and the third trimesters of gestation. The effects were demonstrated
for men and women and for unipolar and bipolar affective disorders. CONCLUSIONS:
These results provide support for the authors' previous findings on the association
between middle to late gestational famine and affective disorder." [Abstract]
TA, Ogura A, Hirai T, Fujihara S, Kitamura T, Takahashi K.
parental separation experiences among patients with bipolar disorder and major
depression: a case-control study.
J Affect Disord 1999
"BACKGROUND: Although the association between childhood
parental loss and later development of mood disorder has received much research
interest in the past, the results obtained and conclusions drawn have been various,
and inconsistent with each other. The present study aims to examine this old,
yet unresolved, question among the Japanese. METHODS: Patients with bipolar disorder
(n = 73) and unipolar depression (n = 570) and community healthy controls (n =
122) were examined as to their psychopathology and childhood parental loss experiences
with semi-structured interviews. RESULTS: Stratified for sex and age, no statistically
significant difference was observed in the incidence of paternal or maternal death
or separation before age 16 between bipolar patients and healthy controls. Female
patients with unipolar depression under the age of 54 experienced significantly
more maternal loss than the corresponding controls. This excess in loss appeared
to be largely due to the patients experiencing separation from their mothers.
CONCLUSION: Our findings concerning bipolar disorder have replicated the previous
two studies reported in the literature. Those concerning unipolar depression appear
to be in line with several recent studies on the subject but, as stated, many
discrepant findings can also be found in the literature." [Abstract]
L, Lundstrom O, Aberg-Wistedt A, Mathe AA.
Social support in bipolar
disorder: its relevance to remission and relapse.
Disord. 2003 Apr;5(2):129-37.
"OBJECTIVES: While an association between
low-level social support and depression has been found in many studies, its relevance
in bipolar illness has been rarely investigated. The aim of this study was to
investigate the effects of social support in the remission and relapse of bipolar
disorder. METHODS: We obtained ratings from 94 stabilized bipolar patients using
two different questionnaires that measure perceived social support: the Interview
Schedule for Social Interaction and the Interpersonal Support Evaluation List.
RESULTS: Significantly lower social support was found in patients in partial recovery
compared with those in full recovery (p = 0.003). Patients who relapsed during
a 1-year prospective follow-up period perceived a significantly lower level of
social support than patients with no relapse (p = 0.012). CONCLUSIONS: Bipolar
patients with full interepisode remission perceive more social support than those
who do not achieve full remission. Poor social support may increase the risk of
relapse in bipolar disorder." [Abstract]
KJ, Byrne M, Mortensen PB.
Risk factors in relation to an emergence
of bipolar disorder: a systematic review.
"OBJECTIVE: There is a consensus that genetic factors
are important in the causation of bipolar disorder (BPD); however, little is known
about other risk factors in the aetiology of BPD. Our aim was to review the literature
on such risk factors - risk factors other than family history of affective disorders
- as predictors for the initial onset of BPD. METHODS: We conducted a literature
search using the MEDLINE, PsycINFO and EMBASE databases. We selected factors of
interest including demographic factors, factors related to birth, personal, social
and family backgrounds, and history of medical conditions. The relevant studies
were extracted systematically according to a search protocol. RESULTS: We identified
approximately 100 studies that addressed the associations between antecedent environmental
factors and a later risk for BPD. Suggestive findings have been provided regarding
pregnancy and obstetric complications, winter-spring birth, stressful life events,
traumatic brain injuries and multiple sclerosis. However, evidence is still inconclusive.
Childbirth is likely to be a risk factor. The inconsistency across studies and
methodological issues inherent in the study designs are also discussed. CONCLUSION:
Owing to a paucity of studies and methodological issues, risk factors of BPD other
than family history of affective disorders have generally been neither confirmed
nor excluded. We call for further research." [Abstract]
Jablensky AV, Morgan V, Zubrick SR, Bower C, Yellachich LA
Pregnancy, delivery, and neonatal complications in a population cohort of women with schizophrenia and major affective disorders.
Am J Psychiatry. 2005 Jan;162(1):79-91.
OBJECTIVE: This study ascertained the incidence of complications during pregnancy, labor, and delivery and the neonatal characteristics of infants born to women with schizophrenia, bipolar disorder, or major depression in a population-based cohort. METHOD: Based on records linkage across a psychiatric case register and prospectively recorded obstetric data, the study comprised women with schizophrenia or major affective disorders who had given birth to 3,174 children during 1980-1992 in Western Australia. A comparison sample of 3,129 births to women without a psychiatric diagnosis was randomly selected from women giving birth during 1980-1992. Complications were scored with the McNeil-Sjöström Scale. Odds ratios were calculated for specific reproductive events. RESULTS: Both schizophrenic and affective disorder patients had increased risks of pregnancy, birth, and neonatal complications, including placental abnormalities, antepartum hemorrhages, and fetal distress. Women with schizophrenia were significantly more likely to have placental abruption, to give birth to infants in the lowest weight/growth population decile, and to have children with cardiovascular congenital anomalies. Neonatal complications were significantly more likely to occur in winter; low birth weight peaked in spring. Complications other than low birth weight and congenital anomalies were higher in pregnancies after psychiatric illness than in pregnancies preceding the diagnosis. CONCLUSIONS: While genetic liability and gene-environment interactions may account for some outcomes, maternal risk factors and biological and behavioral concomitants of severe mental illness appear to be major determinants of increases in reproductive pathology in this cohort. Risk reduction in these vulnerable groups may be achievable through antenatal and postnatal interventions. [Abstract]
R, Johansson C, Kieseppa T, Partonen T, Koskenvuo M, Kaprio J, Lonnqvist J.
changes, sleep length and circadian preference among twins with bipolar disorder.
Psychiatry. 2003 Jun 9;3(1):6. Epub 2003 Jun 09.
"BACKGROUND: We aimed
at studying the seasonal changes in mood and behaviour, the distribution of hospital
admissions by season, and the persistence of the circadian type in twins with
bipolar disorder and their healthy co-twins. METHODS: All Finnish like-sex twins
born from 1940 to 1969 were screened for a diagnosis of bipolar type I disorder.
The diagnosis was assessed with a structured research interview, and the study
subjects (n = 67) filled in the Seasonal Pattern Assessment Questionnaire (SPAQ)
and the Morningness-Eveningness Questionnaire (MEQ). For studying the persistence
of the habitual sleep length and circadian type, we used data derived from the
Finnish Twin Cohort Questionnaire (FTCQ). Bipolar twins were compared with their
healthy co-twins. RESULTS: Bipolar twins had greater seasonal changes in sleep
length (p = 0.01) and mood (p = 0.01), and higher global seasonality scores (p
= 0.03) as compared with their co-twins with no mental disorder. Sunny days (p
= 0.03) had a greater positive effect on wellbeing in the bipolar than healthy
co-twins. CONCLUSIONS: Our results support the view that bipolar disorder is sensitive
to the environmental influence in general and to the seasonal effect in specific.
Exposure to natural light appears to have a substantial effect on wellbeing in
twins with bipolar disorder." [Full
Lee HJ, Kim L, Joe SH, Suh KY.
of season and climate on the first manic episode of bipolar affective disorder
Psychiatry Res 2002 Dec 15;113(1-2):151-9
"The first manic episodes out of 152 bipolar disorder patients were investigated,
in subjects who were admitted in two hospitals in Seoul between 1996 and 1999.
Correlations between the monthly climate variables and the first monthly manic
episodes indicated that the first manic episodes peaked in 25 cases during March.
The mean monthly hours of sunshine and sunlight radiation correlated significantly
with manic episodes. Separating the patients into two groups, namely, with and
without major depressive episode, only the occurrence of manic episodes with major
depressive episode was significantly correlated with mean monthly hours of sunshine.
Separating the subjects by gender, the monthly first manic episodes was significantly
correlated with the intensity of sunlight radiation in female patients only. These
findings suggested that increasing the duration and intensity of sunlight could
facilitate breakdown into the manic episodes." [Abstract]
A, Levitt AJ, Boyle M.
Influence of season and latitude in a community
sample of subjects with bipolar disorder.
Can J Psychiatry.
"OBJECTIVE: To report on the prevalence of seasonal
bipolar disorder (BD) and the impact of latitude in a community sample in the
province of Ontario. METHOD: This study used the telephone-administered Depression
and Seasonality Interview. Exact latitude was determined for each participant.
RESULTS: Overall, 14 of 62 (22.6%) subjects with BD had the seasonal subtype of
BD. Latitude did not appear to influence the proportion of subjects with the seasonal
subtype. CONCLUSIONS: We identified a seasonal pattern of illness in a proportion
of subjects with BD." [Abstract]
Nath J, Sagar R.
disorder due to hyperthyroidism.
Acta Psychiatr Scand 2001
Jul;104(1):72-3; discussion 74-5
"OBJECTIVE: Bipolar disorder starts
typically in early age and late-onset cases are rare. Late-onset cases are more
likely to have comorbid medical illnesses responsible for them. This case report
highlights late-onset bipolar disorder due to hyperthyroidism. METHOD: A 65-year-old
patient of bipolar disorder has been described. RESULT: Physical examination and
laboratory investigations detected presence of hyperthyroidism and the patient
was treated with antithyroid and anxiolytics. CONCLUSION: A thorough examination
and investigation are required in late-onset cases of bipolar disorder to rule
out secondary causes. Definitive antimanic agents or mood stabilizers may not
be required in such cases." [Abstract]
Y, Oshima I, Okagami K.
Seasonality of birth in patients with mood
disorders in Japan.
J Affect Disord 2000 Jul;59(1):41-6
"BACKGROUND: Findings about seasonality of birth in individuals with mood
disorders have been inconsistent. METHODS: Data were collected from the governmental
statistics, the Patient Survey in Japan in 1996. The number of patients with mood
disorders was 13,969. We obtained information about each patient's date of birth,
sex, and diagnosis according to ICD-10. Distributions of monthly birth numbers
of patients with mood disorders were compared to those of the general population.
RESULTS: Birth excess was observed from winter to early-spring in both sexes,
compared to births of the general population. The magnitude of the excess was
larger in females than in males. Although the same tendencies were observed in
patients with bipolar disorder and depressive disorder, the differences were more
marked in females. Limitations: Insufficient birth data in the general population
before 1940 and hospital diagnosis. CONCLUSION: Among Japanese patients with mood
disorders, there are excess births from winter to early-spring, compared to the
general population. This difference is more marked in females than in males."
[Clinical and prognostic significance of seasonal factor in endogenous
Zh Nevrol Psikhiatr Im S S Korsakova. 2002;102(8):14-7.
study aimed at determination of clinical and prognostic significance of seasonal
factor in endogenous maniac state development. Using clinico-psychopathological
and clinical follow-up study, 32 patients (30 women and 2 men) aged 20-50 years
with seasonal endogenous mania were examined. Seasonal mania developed in 12 patients
with bipolar affective disorder, in 13 patients with schizoaffective psychosis
and 7 patients with attack-like schizophrenia (F31.1 - F31.6, F25 and F20.02 +
F25 ICD-10 items respectively). Seasonal maniac state was shown to be a significant
clinical symptom that might be regarded as a prognostic factor. In patients with
bipolar disorder--with a prevalence of both mania and depression-seasonal mania
development in autumn-winter period was a favourable prognostic trait, being observed
mainly in manic depressive psychosis. In spring-summer mania, prognosis was less
favourable and was preferentially found in schizoaffective psychosis and attack-like
M, Bertrand J, Triffaux JM, Troisfontaines B, Kempeneers JL.
of heredity, sex and season on the type of episode of bipolar disorder]
Rev Med Liege 2002 Mar;57(3):171-5
"The aim of this work was to investigate
if sex, age, family history, season and hypothyroidism have any influence on the
type of episodes (manic, depressive, mixed) seen in bipolar patients. This retrospective
study concerns a sample of 208 patients with a diagnosis of bipolar disorder (type
I or II), who were admitted in one of two psychiatric centers between July 1996
and June 2000. The sex-ratio was 2.8 females for 1 male. Sex, family history and
hypothyroidism were not associated with any type of episode. A higher percentage
of depressive episodes was observed in the patients who were older than 50 and
the average age of depressive patients was higher than that of other patients.
There was no seasonal pattern in this study and the season did not influence the
type of episode. The results indicate no influence of sex, season, family history
and hypothyroidism on the type of episode presented. On the opposite, age seems
to favour depression episode." [Abstract]
S, Hibbeln JR.
Cross-national comparisons of seafood consumption
and rates of bipolar disorders.
Am J Psychiatry. 2003 Dec;160(12):2222-7.
The authors sought to determine if greater seafood consumption, a measure of omega-3
fatty acid intake, is associated with lower prevalence rates of bipolar disorder
in community samples. METHOD: Lifetime prevalence rates in various countries for
bipolar I disorder, bipolar II disorder, bipolar spectrum disorder, and schizophrenia
were identified from population-based epidemiological studies that used similar
methods. These epidemiological studies used structured diagnostic interviews with
similar diagnostic criteria and were population based with large sample sizes.
Simple linear and nonlinear regression analyses were used to compare these prevalence
data to differences in apparent seafood consumption, an economic measure of disappearance
of seafood from the economy. RESULTS: Simple exponential decay regressions showed
that greater seafood consumption predicted lower lifetime prevalence rates of
bipolar I disorder, bipolar II disorder, and bipolar spectrum disorder. Bipolar
II disorder and bipolar spectrum disorder had an apparent vulnerability threshold
below 50 lb of seafood/person/year. The absence of a correlation between lifetime
prevalence rates of schizophrenia and seafood consumption suggests a specificity
to affective disorders. CONCLUSIONS: These data describe a robust correlational
relationship between greater seafood consumption and lower prevalence rates of
bipolar disorders. These data provide a cross-national context for understanding
ongoing clinical intervention trials of omega-3 fatty acids in bipolar disorders."