Serum neurotrophin-3 is increased during manic and depressive episodes in bipolar disorder

Accumulating evidence suggest that neural changes and cognitive impairment may accompany the course of bipolar disorder. Such detrimental effects of cumulative mood episodes may be related to changes in neurotrophins that take place during mood episodes but not during euthymic phases. The present study investigated serum neurotrophin-3 (NT-3) levels in patients with bipolar disorder during manic, depressed, and euthymic states, using an enzyme-linked immunosorbent assay (sandwich-ELISA). Serum NT-3 levels were increased in manic (p<0.001) and depressed (p<0.001) BD patients, as compared with euthymic patients and normal controls. These findings suggest that the NT-3 signaling system may play a role in the pathophysiology of BD.     

Serum brain-derived neurotrophic factor is decreased in bipolar disorder during depressive and manic episodes

Genetic and pharmacological studies have suggested that brain-derived neurotrophic factor (BDNF) may be associated with the pathophysiology of bipolar disorder (BD). The present study investigated serum BDNF levels in manic, depressed, euthymic BD patients and in matched healthy controls, using an enzyme-linked immunosorbent assay (sandwich-ELISA). Serum BDNF levels were decreased in manic (p = 0.019) and depressed (p = 0.027) BD patients, as compared with euthymic patients and controls. Serum BDNF levels were negatively correlated with the severity of manic (r = −0.37, p = 0.005) and depressive (r = −0.30, p = 0.033) symptoms. These findings further support the hypothesis that the BDNF signaling system may play a role in the pathophysiology of BD.     

Increased serum glial cell line-derived neurotrophic factor immunocontent during manic and depressive episodes in individuals with bipolar disorder

Glial cell line-derived neurotrophic factor (GDNF) is a neurotrophic factor from the transforming growth factor β family, which plays a role in the development and function of hippocampal cells. Preclinical studies suggest that changes in neurotrophic growth factor systems might be involved in the pathophysiology of mood disorders including bipolar disorder (BD) [E.J. Nestler, M. Barrot, R.J. DiLeone, A.J. Eisch, S.J. Gold, L.M. Monteggia, Neurobiology of depression, Neuron 34 (2002) 13–25]. This is the first study to analyze GDNF immunocontent in BD subjects across different mood states, including mania, depression, and remission (euthymia). Fourty-four bipolar patients (14 depressed, 15 manic, and 15 euthymic) and 14 healthy controls, diagnosed according to the Structural Clinical Interview for DSM-IV were studied. Serum GDNF immunocontent was measured using Western blotting. Serum GDNF immunocontent was increased in manic (F = 42.31; p = 0.001; one-way ANOVA) and depressed (F = 42.31; p = 0.004; one-way ANOVA) bipolar patients, but not in euthymic patients as compared with controls. Our results indicate that changes in GDNF immunocontent occur during acute major affective episodes in bipolar subjects. These results further support the role of neurotrophins in the pathophysiology of bipolar disorder. Whether the observed increase in GDNF immunocontent correspond to a pathological or an adaptive response remains to be determined.     

Adult attachment in bipolar 1 disorder

Objectives. To determine how security of adult attachment style is related to the mania, major depression and euthymic mood states in bipolar 1 (BP1) disorder. Design. An observational cross‐sectional study. Method. One hundred and seven BP1 patients (34 in a manic type episode, 30 in major depressive episode, and 43 in remission) and 41 healthy controls similar in age, gender, reading age, and education were recruited. The groups were compared on self‐reported mean and preferred attachment style controlling for psychiatric comorbidity. Results. Preferred attachment style was insecure in 84 (78%) BP1 patients but only 13 (32%) healthy controls (χ²=34.3, df=3, and p<.001). Healthy controls reported higher secure attachment, lower anxious, and lower preoccupied attachment scores than all groups of patients with bipolar disorder, although the scores for secure attachment in mania and preoccupied attachment in euthymic patients were not significantly different from healthy controls. Overall, within the bipolar groups, anxious attachment style varied little with mood but mania was associated with higher secure and preoccupied attachment style, and depression with higher preoccupied and lower dismissing attachment style scores. Conclusions. Insecure attachment is found in most patients with BP1 disorder. Attachment style is affected by mood episodes so it should be assessed when a patient with bipolar disorder is in remission with minimal residual depressive or manic symptoms.     

Trait impulsivity in patients with mood disorders

BACKGROUND: Impulsivity is a key component of the manic behavior of bipolar disorder and is reported to occur in bipolar patients as a stable characteristic, i.e. a trait. Nevertheless, impulsivity has not been widely studied in depressed bipolar patients. We assessed impulsivity in depressed and euthymic bipolar and unipolar patients and healthy controls. We hypothesized that bipolar subjects would have higher levels of trait impulsivity than the comparison groups. METHODS: Twenty-four depressed bipolar, 24 depressed unipolar, 12 euthymic bipolar, and 10 euthymic unipolar patients, as well as 51 healthy subjects were evaluated with the Barratt Impulsiveness Scale (BIS). Analysis of covariance with age and sex as covariates was used to compare mean group differences. RESULTS: Depressed bipolar, euthymic bipolar, and depressed unipolar patients did not differ, and showed greater impulsivity than healthy controls on all of the BIS scales. Euthymic unipolar patients scored higher than healthy controls only on motor impulsivity. LIMITATIONS: Higher number of past substance abusers in the bipolar groups, and no control for anxiety and personality disorders, as well as small sample sizes, limit the reach of this study. CONCLUSIONS: This study replicates prior findings of stable trait impulsivity in bipolar disorder patients, and extends them, confirming that this trait can be demonstrated in depressed patients, as well as manic and euthymic ones. Trait impulsivity may be the result of repeated mood episodes or be present prior to their onset, either way it would influence the clinical presentation of bipolar disorder.     

State-dependent decrease in levels of brain-derived neurotrophic factor in bipolar disorder: A meta-analytic study

Evidence has suggested a role of brain-derived neurotrophic factor (BDNF) in the pathogenesis of bipolar disorder (BD). Recent studies have examined BDNF levels in BD patients, but showed inconsistent results. In current study, meta-analyses by random-effects model were performed to compare blood BDNF levels between BD patients and healthy controls, and examine patients based on different affective status (manic, depressed, or euthymic state). Fifteen studies from 10 citations were included into the analysis. Pooling of results from all studies indicated that, overall, patients with BD had a lower level of BDNF than healthy controls (p = 1 × 10⁻⁴). But when separating these studies based on different affective status, it showed that the significance existed only when comparing patients in manic (p = 0.0008) or depressed (p = 0.02) state with controls, but not in euthymic state (p = 0.25). In addition, BDNF level was significantly increased after pharmacological treatment of manic state (p = 0.01). These findings indicate that BDNF levels are abnormally reduced in manic and depressed states of BD, and the reduced level in manic state increases after treatment. They suggest a role of blood BDNF level as a state-dependent biomarker of bipolar disorder.     

Predominant polarity in bipolar disorder: diagnostic implications

BACKGROUND: It has been reported that patients with bipolar disorder (BD) remain about 10 years symptomatic before the correct diagnosis is made. This fact is particularly important for patients with predominantly depressed polarity who tend to be diagnosed as suffering from unipolar major depressive disorder and treated with antidepressants. The present study was carried out to assess clinical differences between predominantly manic and depressed BD patients with a special focus on the time that patients remained undiagnosed. METHODS: Clinical and socio-demographic characteristics were obtained from a sample of 149 euthymic bipolar outpatients. Patients were divided into depressive or manic predominance of polarity. Clinical features, number of years undiagnosed (NYU) and occupational functioning were assessed in the two groups. RESULTS: Forty-five patients were classified as a "Depressive Polarity" whilst forty-seven were considered as "Manic Polarity". Depressive Polarity was associated with a longer delay to be diagnosed (F=14.43, df=89, p=0.001). The predominantly depressive patients tended to present a depressive onset of illness, earlier age of onset, longer duration of illness and higher number of suicide attempts than manic polarity patients. CONCLUSION: There was a marked clinical difference between predominantly manic and depressive bipolar patients. Predominantly depressive polarity is associated with a longer delay in receiving a correct diagnosis and effective treatment which has an important impact on the management of the illness.     

Oxidative stress parameters in unmedicated and treated bipolar subjects during initial manic episode: a possible role for lithium antioxidant effects

Studies have proposed the involvement of oxidative stress and neuronal energy dysfunctions in the pathophysiology of bipolar disorder (BD). This study evaluates plasma levels of the oxidative/energy metabolism markers, thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD), catalase (CAT), and neuron-specific enolase (NSE) during initial episodes of mania compared to controls in 75 subjects. Two groups of manic subjects (unmedicated n=30, and lithium-treated n=15) were age/gender matched with healthy controls (n=30). TBARS and antioxidant enzymes activity (SOD and CAT) were increased in unmedicated manic patients compared to controls. Conversely, plasma NSE levels were lower during mania than in the controls. In contrast, acute treatment with lithium showed a significant reduction in both SOD/CAT ratio and TBARS levels. These results suggest that initial manic episodes are associated with both increased oxidative stress parameters and activated antioxidant defenses, which may be related to dysfunctions on energy metabolism and neuroplasticity pathways. Antioxidant effects using lithium in mania were shown, and further studies are necessary to evaluate the potential role of these effects in the pathophysiology and therapeutics of BD.     

Attention orienting and inhibitory control across the different mood states in bipolar disorder: An emotional antisaccade task

An antisaccade experiment, using happy, sad, and neutral faces, was conducted to examine the effect of mood-congruent information on inhibitory control (antisaccade task) and attentional orienting (prosaccade task) during the different episodes of bipolar disorder (BD) – manic (n = 22), depressive (n = 25), and euthymic (n = 24). A group of 28 healthy controls was also included. Results revealed that symptomatic patients committed more antisaccade errors than healthy individuals, especially with mood-congruent faces. The manic group committed more antisaccade errors in response to happy faces, while the depressed group tended to commit more antisaccade errors in response to sad faces. Additionally, antisaccade latencies were slower in BD patients than in healthy individuals, whereas prosaccade latencies were slower in symptomatic patients. Taken together, these findings revealed the following: (a) slow inhibitory control in BD patients, regardless of their episode (i.e., a trait), and (b) impaired inhibitory control restricted to symptomatic patients (i.e., a state)     

Mismatch between self-reported quality of life and functional assessment in acute mania: a matter of unawareness of illness?

BACKGROUND: Studies addressing self-reported quality of life (QoL) in acute mania are scarce and inconsistent. While it has been suggested that there is some disagreement between objective measures and subjective QoL as reported by acutely manic patients, this issue has not been systematically studied. This study aims to investigate the self-reported QoL in manic, depressed, and euthymic BD subjects, as compared to matched healthy controls. METHODS: One-hundred and twenty type-I bipolar patients (40 manic, 40 depressed, and 40 euthymic) and 40 matched controls were studied. Self-reported QoL was assessed using the World Health Organization's Quality of Life Instrument-Short Version (WHOQOL-BREF). Objective functioning was assessed using the Global Assessment of Functioning (GAF), and depressive and manic symptoms were assessed using the Hamilton Depression Rating Scale-17 items (HDRS) and the Young Mania Rating Scale (YMRS), respectively. RESULTS: Manic patients presented the lowest GAF measures but reported same overall QoL as euthymic patients and controls, and better QoL than depressed patients. Within the manic subgroup, there was a significant inverse correlation between psychological QoL and GAF scores (r=-0.54; p=0.001). LIMITATIONS: The cross-sectional design and the lack of control for potential comorbid conditions are the major limitations of the present study. CONCLUSIONS: Our findings suggest that this mismatch between objective and subjective measures during acute mania may be associated with a lack of insight or awareness of their own illness.     

Does first episode polarity predict risk for suicide attempt in bipolar disorder?

BACKGROUND: Defining bipolar disorder (BD) subtypes with increased risk of suicidal behavior may help clinical management. We tested the hypothesis that the polarity of a patient's first mood episode would be a marker for BD subtypes with differential risk for suicidality. METHODS: One hundred thirteen subjects with DSM-IV defined BD were classified based on whether their first reported episode was manic/hypomanic (FM) or depressed (FD). They were compared on demographic and clinical variables. Logistic regression adjusting for potential confounds tested the association between first episode polarity and history of suicide attempt. RESULTS: Multiple logistic regression analysis showed that FD group membership was associated with eightfold odds of a past suicide attempt, adjusting for years ill and total number of lifetime major depressive episodes. LIMITATIONS: Sample size, retrospective design, recall bias, assessment during a mood episode, and imprecise recall of hypomania. CONCLUSIONS: Polarity of patients' first reported mood episode suggested a depression-prone subtype with a greater probability of past suicide attempt. The FM group had more alcoholism and psychosis, but less likelihood of past suicide attempt. Validation of these putative subtypes requires prospective study.     

Does latitude as a zeitgeber affect the course of bipolar affective disorder?

Background

Bipolar disorder (BD) is characterized by recurrent episodes of mood dysregulations and depression is considered as the most frequent form of relapse. However, there is some evidence that in tropical countries, the course might be different with fewer depressive episodes. This study aims to examine the frequency of depressive and manic episodes in a sample of subjects with BD from India.

Methods

Index subjects and a reliable informant (a family member) were interviewed with Diagnostic Interview for Genetic studies and a life chart was drawn to ascertain the episodes of illness in addition to reviewing their clinical case records. The mean total episode frequency and the mean manic and depressive episode frequency were estimated for this study.

Results

Data on the total episode number and number of manic and depressive episodes separately was available in 439 subjects. The subjects had been ill for 7.45 years, had experienced an average of 3.29 episodes of mania and 1.08 episodes of depression. Thus episodes of mania were seen to be more frequent.

Conclusion

It has been increasingly recognized that circadian rhythm abnormalities could play an important role in the relapse and symptom expression of bipolar disorder. The mania predominance in the course of BD in this population contrasts from the depressive predominance in other studies. We suggest that this phenomenon could be a function of latitudinal gradient in the expression of BD using the zeitgeber hypothesis.     

Do changes in subjective sleep and biological rhythms predict worsening in postpartum depressive symptoms? A prospective study across the perinatal period

Abnormalities of sleep and biological rhythms have been widely implicated in the pathophysiology of major depressive disorder (MDD) and bipolar disorder (BD). However, less is known about the influence of biological rhythm disruptions across the perinatal period on postpartum depression (PPD). The objective of this study was to prospectively evaluate the relationship between subjective changes in both sleep and biological rhythms and worsening of depressive symptoms from pregnancy to the postpartum period in women with and without mood disorders. Eighty-three participants (38 euthymic women with a history of a mood disorder and 45 healthy controls) were studied. Participants completed subjective assessments of sleep (Pittsburgh Sleep Quality Index), biological rhythm disturbances (Biological Rhythms Interview of Assessment in Neuropsychiatry), and depressive symptoms (Edinburgh Postnatal Depression Scale) prospectively at two time points: third trimester of pregnancy and at 6–12 weeks postpartum. Multivariate regression analyses showed that changes in biological rhythms across the perinatal period predicted worsening of depressive symptoms in both groups. Moreover, women with a history of a mood disorder showed higher levels of sleep and biological rhythm disruption during both pregnancy and the postpartum period. These findings suggest that disruptions in biological rhythms during the perinatal period increase the risk for postpartum mood worsening in healthy pregnant as well as in pregnant women with a history of mood disorders.     

Towards a reconceptualization of mixed states, based on an emotional-reactivity dimensional model

BACKGROUND: DSM-IV criteria for mixed states may be too restrictive and may actually exclude patients who do not meet the full criteria for a manic and depressive state. Using this DSM-IV definition, many patients who are considered depressed may have mixed features, which can explain why some bipolar depressive states can worsen with antidepressants and can be improved by mood stabilizers or atypical antipsychotics. A dimensional approach not exclusively focused on the tonality of affect would help to define a broader entity of mixed states. The aim of this study was to apply a dimensional model to bipolar episodes and to assess the overlap between the groups defined using this model and using categorical diagnosis. METHOD: We assessed 139 DSM-IV acutely ill bipolar I patients with MAThyS (Multidimensional Assessment of Thymic States by Henry et al. in press), a scale that assesses five quantitative dimensions exploring excitatory and inhibition processes, and that is not focused on tonality of mood but on emotional reactivity. We studied the relationship between clusters defined by statistical analyses and DSM-IV bipolar mood states. RESULTS: This study showed the existence of three clusters. Cluster 1 was characterized by an inhibition in all dimensions and corresponded to the depressive cluster (more than 90% of patients met the criteria for DSM-IV Major Depressive Episode (MDE)). Cluster 2 showed a general excitation and was mainly DSM-IV manic or hypomanic patients (90%). Cluster 3 (Mixed) was more complex and the diagnosis included MDE (56%) in most of the cases associated with manic or hypomanic symptoms, mixed states (18%) defined by DSM-IV criteria, and manic or hypomanic states (25%). Emotional reactivity was relevant to distinguish Cluster 1 (Depressive), exhibiting emotional hypo-reactivity, from Cluster 2 (Manic) and 3 (Mixed), characterized by emotional hyper-reactivity. Sadness was reported equally in all three clusters. CONCLUSION: A dimensional approach using the concept of emotional reactivity seems appropriate to define a broad mixed state entity in patients who would be diagnosed with MDE according to DSM-IV. Further studies are needed to test the relevance of this model in therapeutic strategies.     

A Commentary on "Sleep Disturbance in Bipolar Disorder"

Sleep disturbances are among the most common clinical features of bipolar affective disorder and are typically present in manic, hypomanic, mixed, and depressive episodes. The processes that regulate sleep are relevant to the pathophysiology of bipolar illness and further study of these processes may help to elucidate fundamental associations with central nervous system arousal and cerebral metabolism. Among the various therapeutic interventions that are used to treat insomnia associated with bipolar affective disorder, the strategies and approaches of behavioral sleep medicine warrant greater attention.     

A prospective study of the transition rates of subthreshold (hypo)mania and depression in the general population

BACKGROUND: Previous work suggests that subthreshold depression and subthreshold (hypo)mania are common, although little is known about the prognosis in terms of transition to clinical disorder. This paper presents data on the temporal relationship between subthreshold and clinical expression of mood phenotypes. METHOD: In a random general population sample of 7076 individuals, symptoms of depression and (hypo)mania were measured with the Composite International Diagnostic Interview (CIDI) at baseline, after 1 year, and 2 years later. RESULTS: At baseline, the lifetime prevalences of depressive and (hypo)manic symptoms were 17.2% and 1.2% respectively. Predictive values of mood symptoms for a DSM-III-R mood disorder ranged from 14.3% to 50%. (Hypo)manic mood symptoms had much higher predictive values than unipolar manifestations, not only for bipolar disorder but also for major depression. CONCLUSIONS: The subthreshold expressions of depression and (hypo)mania are prevalent and continuous with more severe clinical states. The cross-prediction of mood symptoms may support a continuum from depressive to (hypo)manic symptoms. The high predictive value of (hypo)manic symptoms for mood disorders suggests that the experience of (hypo)manic symptoms is a stronger indicator of vulnerability for mood dysregulation than the experience of depressive symptoms.     

Affective temperaments are associated with specific clusters of symptoms and psychopathology: A cross-sectional study on bipolar disorder inpatients in acute manic,mixed, or depressive relapse

Background

The aim of this study was to assess whether different affective temperaments could be related to a specific mood disorder diagnosis and/or to different therapeutic choices in inpatients admitted for an acute relapse of their primary mood disorder.

Method

Hundred and twenty-nine inpatients were consecutively assessed by means of the Structured and Clinical Interview for axis-I disorders/Patient edition and by the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego auto-questionnaire, Young Mania Rating Scale, Hamilton Scale for Depression and for Anxiety, Brief Psychiatry Rating Scale, Clinical Global impression, Drug Attitude Inventory, Barratt Impulsiveness Scale, Toronto Alexithymia Scale, and Symptoms Checklist-90 items version, along with records of clinical and demographic data.

Results

The following prevalence rates for axis-I mood diagnoses were detected: bipolar disorder type I (BD-I, 28%), type II (31%), type not otherwise specified (BD-NOS, 33%), major depressive disorder (4%), and schizoaffective disorder (4%). Mean scores on the hyperthymic temperament scale were significantly higher in BD-I and BD-NOS, and in mixed and manic acute states. Hyperthymic temperament was significantly more frequent in BD-I and BD-NOS patients, whereas depressive temperament in BD-II ones. Hyperthymic and irritable temperaments were found more frequently in mixed episodes, while patients with depressive and mixed episodes more frequently exhibited anxious and depressive temperaments. Affective temperaments were associated with specific symptom and psychopathology clusters, with an orthogonal subdivision between hyperthymic temperament and anxious/cyclothymic/depressive/irritable temperaments. Therapeutic choices were often poorly differentiated among temperaments and mood states.

Limits

Cross-sectional design; sample size.

Conclusions

Although replication studies are needed, current results suggest that temperament-specific clusters of symptoms severity and psychopathology domains could be described.     

Seasonal variations in bipolar disorder admissions and the association with climate: a population-based study

OBJECTIVE: Although seasonal influences on bipolar disorder admissions have long been observed, the issues of seasonality on different subtypes of mood episodes and the effects of associated climatic parameters remain controversial. This study sets out to examine seasonal variations in bipolar disorder admissions and the association with climate in Taiwan, a subtropical area with fairly constant weather conditions. METHODS: This retrospective population-based study uses the Taiwan National Health Insurance Research Database for 1999-2003, identifying 15,060 admissions for bipolar disorder, comprising of 8631 manic, 2078 depressive and 4351 mixed/unspecified episodes. The auto-regressive integrated moving average model was applied to examine the presence of seasonality and the association with climate in each subtype of mood episodes. RESULTS: Admission peaks were noted during spring/summer, early winter and early spring, for manic, depressive and mixed/unspecified episodes, respectively, while the associations with climatic parameters varied between the subtypes of mood episodes. CONCLUSIONS: Seasonality in bipolar disorder does exist for all subtypes of mood episodes. The distinct seasonal patterns and various associations with the climatic parameters imply different underlying mechanisms for the onset of each subtype of mood episodes. The association between admission rates and certain climatic variables found in this study is informative and could pave the way for future studies aimed at exploring the influence of climate on the psychopathology of bipolar patients as well as the underlying mechanisms.     

High harm avoidance and low self-directedness in euthymic young adults with recurrent, early-onset depression

BACKGROUND: The personality dimensions of harm avoidance (HA) and self-directedness (SD), as measured by the Temperament and Character Inventory (TCI), have been widely associated with depression and there is preliminary evidence that they may represent trait markers for depression. However, many studies in this area are limited by the use of heterogeneous samples of depressed patients and by the confounding effect of depressed mood during personality testing. The current study compares TCI personality dimension scores in a group of euthymic young adults with recurrent early-onset major depressive disorder (RE-MDD) to well-matched euthymic controls. METHODS: Fifty-two young adults with a past history of RE-MDD were recruited from consecutive referrals to a psychiatric clinic at a university health service. Eighty nine controls were also recruited. Euthymia was established in patients by a score of less than 9 on the Hamilton Rating Scale for Depression (HRSD) and in controls by a Becks Depression Inventory (BDI) score of less than 10. All participants completed the TCI-125. RESULTS: Patients and controls were well matched in terms of sociodemographic profile. Euthymic RE-MDD patients scored significantly higher than controls on the temperament dimension of harm avoidance (HA; mean score 14.5 versus 7.8, p<0.0001) and significantly lower than controls on the character dimension of self-directedness (SD; mean score 14.1 versus 19.9, p<0.0001). Covariance analysis suggested that both HA and SD contributed independently to the familial risk of depression. LIMITATIONS: Subjects and controls all came from relatively affluent social backgrounds-these findings may not generalise to more socioeconomically diverse populations. The possibility of a 'scarring effect' of depressive episodes on self-reported personality dimension scores cannot be excluded. CONCLUSIONS: High HA and low SD represent trait markers for liability to recurrent major depressive disorder in young adults. Further research is needed to replicate these findings and to assess the contribution that the experience of depressive episodes makes to self-reported personality dimension scores.     

Increased expression of splicing factor SRp20 mRNA in bipolar disorder patients

BACKGROUND: Variations and defects in alternative splicing are well known to be associated with a variety of human diseases and the stress response. We previously reported a decrease in glucocorticoid receptor (GR) alpha, but not GRbeta in mood disorder patients, suggesting an aberrant alternative splicing mechanism. To examine whether altered RNA splicing may underlie the pathophysiology of mood disorder, we evaluated the expression of a variety of SR protein splicing factors, a family of proteins indispensable for proper alternative splicing, in mood disorder patients. METHODS: We used quantitative real-time PCR to measure expressions of SRp20, SRp30c, SC35, SRp40, SRp46, SRp54, SRp55, SRp75, ASF/SF2, and 9G8 mRNA in peripheral white blood cells of 33 mood disorder patients during a depressive episode. In addition, the expressions of SRp20 and SC35 mRNA were quantified for 78 mood disorder patients in a remissive state, and 32 the first-degree relatives of these mood disorder patients. RESULT: A significant correlation was observed between SRp30c and the GRbeta/GRalpha ratio in control subjects, but not in mood disorder patients. Increased expression of SRp20 but not SRp30c mRNA was observed in bipolar disorder patients in both the depressive and remissive states. Major depressive disorder patients did not show any significant change in mRNA levels of SR proteins. LIMITATION: Subjects were Japanese adults. Patient treatment was not standardized. CONCLUSIONS: These results suggest that aberrant alternative splicing machinery caused by increased SRp20 mRNA expression would be associated with the pathophysiology of bipolar disorder.