Results from a survey conducted by the World Health Organization (WHO) in low-, middle-, and high-income countries show that people with serious mental health disorders earn, on average, one third less than people without mental health issues.

Writing in the British Journal of Psychiatry, Ronald Kessler (Harvard Medical School, Boston, Massachusetts, USA) and team explain that, “although a considerable body of empirical research has used the human capital approach to document adverse societal effects of mental disorders, this research has been carried out largely in a small number of high-income countries.”

They add: “Yet epidemiological data show that mental disorders are common throughout the world.”

To investigate the effects of serious mental illness on earnings in a wider range of countries, the researchers studied data from WHO World Mental Health (WMH) surveys conducted in 10 high- and nine low- and middle-income countries.

All respondents were asked to report their personal earnings in the past 12 months. Mental illness within the past 12 months was assessed via the WHO Composite International Diagnostic Interview using DSM-IV criteria for anxiety and mood disorders, such as bipolar disorder and major depressive disorder.

In total, 101,825 participants were interviewed, with individual country sample sizes ranging from 2372 in The Netherlands to 12,992 in New Zealand.

The researchers found that the prevalence of serious mental illness was significantly higher in high-income countries than in low- and middle-income countries both in the total sample (4.3% vs 3.0%) and considering men (3.5% vs 2.2%) and women (5.0% vs 3.9%) separately.

After accounting for factors such as age, gender, and between-country differences in earnings, the researchers found that people with serious mental illnesses earned an average of 32-33% less in the past 12 months than mentally healthy individuals.

Indeed, serious mental illnesses were associated with a reduction in population-level earnings equivalent to 0.8% of all earnings in high-income countries and 0.3% of all earnings in low- and middle-income countries.

“These comparisons make it clear that mental disorders are associated with massive losses of productive human capital not only at the individual level… but also at the societal level in the WMH countries,” Kessler and team conclude.

“Decisions about healthcare resource allocation should take these costs into consideration.”

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

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Prenatal exposure to tobacco smoke is associated with an increased risk for psychiatric disorders in adolescence and young adulthood, researchers have found.

“Smoking during pregnancy has many harmful effects on the growing fetus, including impairment of fetal growth,” explain Mikael Ekblad (Turku University Hospital, Finland) and team. “In recent years, smoking exposure has also been described to have harmful effects on the developing brain.”

To investigate whether maternal smoking during pregnancy increases the risk for psychiatric morbidity in late adolescence and young adulthood, the researchers studied data on all 175,869 singleton children without major congenital abnormalities who were born in Finland between 1987 and 1989.

Information on maternal smoking was collected by midwives during antenatal care, and data on gestational age, maternal age, birth weight, parity, and other variables were derived from the Finnish Medical Birth Register.

The Finnish Hospital Discharge Register was used to identify all psychiatric diagnoses among the children through to 2007, and the Cause-of-Death Register was used to identify all those who died during the 20-year period.

Overall, 15.3% of mothers reported smoking during pregnancy and 15.0% of children received a psychiatric diagnosis resulting in hospital care during the study period.

The researchers found that, compared with children born to women who did not smoke during pregnancy, those born to women who smoked 1-9 cigarettes a day were 1.53 times more likely to develop a psychiatric disorder, while those born to women who smoked 10 or more cigarettes a day were 1.85 times more likely to develop such a disorder.

The increased risk for psychiatric disorders associated with prenatal tobacco smoke exposure remained significant after accounting for potential confounding factors, such as a family history of such conditions.

It was also significant for all psychiatric diagnoses except schizophrenia, with the strongest effects seen for behavioral and emotional disorders and those due to psychoactive substance use.

Prenatal exposure to 10 or more cigarettes a day was also associated with significantly increased total mortality, at an adjusted odds ratio of 1.69.

Ekblad and colleagues conclude in the Archives of General Psychiatry: “Prenatal smoking exposure is associated with an increased risk of psychiatric morbidity in childhood, adolescence, and young adulthood.”

They add: “It might be possible to reduce psychiatric morbidity by reducing smoking exposure during pregnancy.”

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

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Different risk factors are associated with the onset and persistence of subthreshold mania and depression symptoms in young people, researchers have found.

“Little is known about the factors that influence persistence of subthreshold expression of bipolar psychopathology,” explain Marieke Wichers (Maastricht University, The Netherlands) and team.

They add: “Insights into the causes of persistence would facilitate the identification of subjects at risk in an early stage of the development of psychopathology and make early intervention possible.”

The researchers therefore assessed data from the Early Developmental Stages of Psychopathology study (EDSP) on 705 young people from Munich, Germany, who were aged 14-17 years at baseline.

The participants were interviewed at baseline and at regular intervals over an average follow-up period of 8.3 years using the Munich-Composite International Diagnostic Interview (DIA-X/M-CIDI), an updated version of the World Health Organization’s CIDI version 1.2.

Mood symptoms were assessed using 28 items of the DIA-X/M-CIDI depression and dysthymia section and 11 items of the DIA-X/M-CIDI mania section.

In total, 46 participants had mania symptoms at baseline and follow-up, and of the participants without mania symptoms at baseline, 79 developed such symptoms over follow up.

Analysis revealed that the onset of mania symptoms over follow up was significantly associated with cannabis use (use of the drug on at least five occasions), at an odds ratio (OR) 4.26, and novelty seeking, at an OR of 3.47.

However, none of the risk factors assessed, including family history of (hypo)mania, attention-deficit hyperactivity disorder (ADHD), and experience of trauma, were significantly associated with persistence of mania symptoms. Novelty seeking predicted only transient mania symptoms.

Regarding depression symptoms, 107 participants had such symptoms at baseline and follow up, and of those without depression symptoms at baseline 82 developed such symptoms over follow up.

Onset of depression symptoms was associated with a family history of depression, while persistence of such symptoms was associated with ADHD and harm avoidance. Of note, a family history of depression and trauma predicted a transitory course of such symptoms.

Wichers and team conclude in the journal Acta Psychiatrica Scandinavica: “Different risk factors may operate during onset and persistence of subthreshold mania and depression.

“The differential associations found for mania and depression dimensions suggest partly different underlying mechanisms.”

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

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Around a quarter of patients with fibromyalgia also suffer from bipolar disorder, results from a US study suggest.

Writing in the journal Bipolar Disorders, William Wilke, from the Cleveland Clinic Orthopedic and Rheumatologic Institute in Ohio, and team explain that the prevalence of lifetime depression in patients with fibromyalgia is known to be particularly high, at around 90%, compared with 17% in the general population.

They add that bipolar disorder is known to affect around 1.5% of the general population, but less is known about the prevalence of the condition in fibromyalgia patients.

To investigate, the team studied 128 fibromyalgia patients referred to the Cleveland Clinic between January and June 2005.

All patients were assessed using the Mood Disorder Questionnaire (MDQ) for bipolar disorder, the Beck Depression Inventory (BDI), the Epworth Sleepiness Scale (ESS) for daytime sleepiness, and the Fibromyalgia Impact Questionnaire Disability Index (FIQ-DI).

The researchers found that 25.2% of fibromyalgia patients screened positive for bipolar disorder, with a score of 7 or higher on the MDQ.

Furthermore, 78.1% had clinical depression, as indicated by a BDI score of 10 or higher, and 52.1% reported daytime sleepiness, as indicated by a score of at least 10 on the ESS.

Among the patients with symptomatic depression, nearly one third (32.0%) screened positive for bipolar disorder.

Fibromyalgia patients who screened positive for bipolar disorder were significantly more depressed than those with a negative screen, with scores on the BDI of 26.0 versus 15.0.

Wilke and team conclude: “The most important finding of our study pertains to the high prevalence of a positive screen for bipolar disorder in patients with fibromyalgia. With the exception of more severe depression, no other clinical clues were present to help identify patients with fibromyalgia and bipolar disorder.”

They add: “We urge that bipolar disorder risk be carefully assessed in all patients with fibromyalgia prior to initiation of drug therapy, particularly since norepinephrine serotonin reuptake inhibitors may carry elevated risk for induction of mania.”

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

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Transient manic symptoms (TMS) are associated with an increased risk for conversion to bipolar spectrum disorder (BPSD) in children with depressive spectrum disorders (DSD), study results show.

The findings also suggest that early multi-family psycho-educational psychotherapy may protect against conversion to BPSD in such children.

Writing in the journal Bipolar Disorders, Mary Fristad (Ohio State University, Columbus, USA) and colleagues explain: “No studies to date have longitudinally assessed the clinical importance of TMS in children with DSD to determine whether these transient subthreshold manifestations later progress to a recognized BPSD.”

To address this, the team studied 165 children, aged an average of 9.9 years, with mood disorders who participated in the Multi-Family Psychoeducational Psychotherapy (MF-PEP) treatment study. Of these, 37 had DSD plus TMS, 13 had DSD alone, and 115 had BPSD.

At baseline, 78 children were randomly assigned to immediately receive MF-PEP while 87 were assigned to a 1-year waiting list for the intervention (controls).

All of the children were assessed using the Children’s Interview for Psychiatric Syndromes-Child, the Mania Rating Scale, and the Children’s Depression Rating Scale-Revised on four occasions over the 18-month study period.

In total, 13 children converted to BPSD during the study period, with the DSD+TMS group having a significantly higher conversion rate (48.0%) than the DSD-alone group (12.5%).

Conversion rates were also significantly higher in the control group (60.0%) than in the intervention group (16.0%).

The researchers note that children who converted to BPSD had greater levels of functional impairment at baseline than those who did not, but there were no significant differences between converters and non-converters regarding clinical presentation, family environment, and family history of mental health disorders.

Also, the use of antidepressants, stimulants, mood stabilizers, antipsychotics, and other medications were not associated with conversion rates.

“TMS are a risk factor for eventual conversion to BPSD,” Fristad and team conclude.

“An additional intriguing finding, which clearly warrants additional investigation, is the suggestion that psycho-educational psychotherapy may be protective for depressed children in staving off potential conversion to BPSD,” they add.

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

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Results from a German study show that a single nucleotide polymorphism (SNP) in the calcium channel, voltage-dependent, L-type, alpha 1C subunit (CACNA1C) gene is associated with brain-function deficits in mentally healthy volunteers.

The findings, published in the Archives of General Psychiatry, also support previous genetic research linking the SNP to bipolar disorder by providing evidence of a “neurogenetic risk mechanism.”

Susanne Erk (Charite Medical University Berlin) and colleagues explain: “Recently, a meta-analysis of three genome-wide association studies reported strong evidence for an association between bipolar disorder and polymorphism rs1006737 located within the CACNA1C gene.”

The CACNA1C gene is involved in controlling calcium influx through Ca_v1.2 channels, which triggers processes that underlie hippocampus-dependent memory.

Hippocampal abnormalities have been repeatedly observed in patients with bipolar disorder, but “a direct demonstration of the role of CACNA1C for human hippocampal function in general and the relevance of these neural systems for heritable risk for bipolar disorder in particular has not been provided,” say Erk and team.

To investigate whether the genetic risk associated with rs1006737 is mediated through hippocampal function, the team genotyped 110 mentally healthy volunteers without a family history of affective disorder or schizophrenia.

Regional brain activation and functional coupling between brain regions was assessed using magnetic resonance imaging while the participants performed an episodic memory task.

In total, 60 participants were rs1006737 GG homozygotes, 41 were GA heterozygotes, and nine were AA homozygotes.

The team found that carriers of the risk allele A had significantly reduced bilateral hippocampal activation during episodic memory recall, as well as reduced functional coupling between left and right hippocampal regions, compared with G homozygotes.

Furthermore, carriers of the risk allele had reduced activation of the subgenual anterior cingulate cortex compared with G homozygotes. This is a region that has previously been associated with affective disorders and the mediation of adaptive stress-related responses, note the researchers.

Carriers of the risk allele also scored significantly higher than G homozygotes on measures of depression, anxiety, obsessive-compulsive thoughts, interpersonal sensitivity, and neuroticism, and these scores correlated negatively with regional brain activation.

“Taken together, our findings show that the recently identified risk variant in the CACNA1C gene is associated with functional effects in the human brain even in the absence of overt disease,” say Erk et al.

“Moreover, these findings identify a system of altered functional activation in the hippocampus and subgenual anterior cingulate cortex that provides the first neural circuit for risk for bipolar disorder supported by genome-wide evidence.”

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

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Scandinavian researchers have found significant correlation between the number of manic episodes experienced and the extent of grey matter volume reduction in patients with bipolar disorder.

“Several investigations using magnetic resonance imaging (MRI) have demonstrated anatomical abnormalities in the brain of patients with bipolar disorder,” explain Carl Ekman (Karolinska Institute, Stockholm, Sweden) and team.

However, they add that few studies have investigated whether such abnormalities, including the loss of grey matter volume, are associated with illness duration, and if specific brain regions are more vulnerable than others to depressive and/or manic episodes.

To investigate further, the researchers enrolled 55 adult patients (60% women) with bipolar I disorder who were free of co-morbid conditions associated with regional cortical volume changes, such as alcohol or drug dependence, attention-deficit hyperactivity disorder, panic disorder, or anorexia.

Information on duration of bipolar illness and lifetime number of mood episodes was gathered from patient interviews and medical records.

All of the patients underwent brain MRI and the resulting images were analyzed using voxel-based morphometry.

After accounting for age and gender, the researchers found that the lifetime number of manic episodes significantly correlated with reductions in local grey matter volume in both the right and left inferior frontal gyrus, corresponding to Brodmann’s area 46.

The lifetime number of depressive episodes or years of illness did not correlate with any changes in grey matter volume, however.

Writing in the journal Acta Psychiatrica Scandinavica, Ekman and team conclude that the findings indicate that “abnormalities in the prefrontal regions appear to develop with repeated affective episodes.”

They add: “To further assess the possibly progressive nature of these reductions in brain tissue, longitudinal studies with repeated scans of clinically homogenous patients with bipolar disorder are required.”

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

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Schizoaffective disorder (SA) is a valid diagnosis in the early phase of psychotic conditions and defines a subgroup of patients with first episode psychotic mania.

“The validity of SA diagnosis has long been a matter of controversy and its delineation from bipolar I disorders has often been questioned,” explain Philippe Conus (Universite of Lausanne, Switzerland) and team.

They add that most studies investigating SA “have been conducted in chronic samples and have therefore been biased towards patients with poorer outcome, which may have hampered the possibility to identify significant differences between both diagnoses.”

To address this, the researchers studied 108 patients in Melbourne, Australia, who presented with a first manic episode with psychotic features between 1989 and 1997.

The patients were assessed at baseline and 12 months after stabilization of symptoms and functional characteristics. At the 12-month assessment, 87 patients met criteria for a diagnosis of bipolar disorder (BD) and 21 met DSM-III-R criteria for an SA bipolar subtype (SAB) diagnosis.

Comparing the two groups of patients, the researchers found that those with SAB had a significantly higher prevalence of first-degree relatives with schizophrenia, at 30.0% versus 10.5%, and lower premorbid adjustment scores (general subscale) of 0.33 versus 0.25, than those with BD.

Patients with SAB had significantly higher scores on the positive symptom subscale of the Brief Psychiatric Rating Scale (BPRS) than those with BD at baseline and at the 12-month assessment, at 12.0 versus 10.1 and 2.2 versus 1.7, respectively. They also had higher scores on the negative symptom subscale of the BPRS than those with BD at these two time points, at 15.6 versus 11.6 and 11.5 versus 9.3, respectively.

Furthermore, SAB patients had a longer prodromal phase (198.8 vs 87.7 days), a longer duration of untreated psychosis (56.3 vs 15.3 days), and remained symptomatic for longer after admission (46.9 vs 25.0 days) than those with BD.

However, regarding psychotic symptoms, only mood incongruent psychotic symptoms and passivity feelings were significantly more frequent in SAB than BD patients, with other psychotic symptoms showing similar frequency in the two groups.

Conus and team conclude in the Journal of Affective Disorders: “Our findings suggest that a distinction between SAB and BD according to criteria proposed in DSM-III-R is valid in patients presenting with a first episode of psychotic mania, and reflects two diagnostic conditions that have distinct premorbid and outcome characteristics.”

They add: “While more research is warranted to explore if other characteristics (brain structure, biological markers) confirm this clinical distinction, our data suggest SAB is a valid diagnosis.”

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

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Patients with bipolar disorder (BD) with an initial mixed mood episode experience greater levels of morbidity over subsequent months than those with an initial episode of mania.

“Mixed-states involve complex admixtures of rapid alternations of mainly excited or mainly depressive states,” explain Ross Baldessarini (Harvard Medical School, Boston, Massachusetts, USA) and team.

They add: “There is growing evidence that early BD mixed states may be followed by particularly severe later morbidity.”

Regarding morbidity after an initial mood episode, they also say that “there appears to be a tendency to consider manic and mixed episodes… as closely related.”

To investigate further, the researchers studied 247 BD patients (54% men), of whom 97 presented with an initial DSM-IV mixed episode and 150 with an initial episode of mania.

Morbidity was assessed on a weekly basis over a follow-up period of 24 months, and included DSM-IV manic, hypomanic, mixed, or major depressive states, as well as less severe dysthymic or dysphoric states that did not meet DSM-IV criteria but appeared to be clinically significant.

The researchers found that patients with an initial mixed episode spent 60.0% of the weeks during follow up in a morbid state compared with 37.8% of follow-up weeks among patients with an initial episode of mania. Indeed, morbidity levels during follow up were 1.59 times greater among patients with an initial mixed episode than among those with an initial episode of mania.

Patients with an initial mixed episode also had 11.9 times more mixed-states, 6.54 times more major depressive episodes, and 1.69 times more dysthymia during follow up than patients presenting with mania.

In contrast, patients with a first episode of mania had significantly more mania and hypomania episodes during follow up than those with an initial mixed episode.

Baldessarini and team summarize: “The present findings indicate strongly that initial mixed-states of DSM-IV type-I BPD were not only followed by more weeks of illness during two years of follow-up, but also much more mixed, depressive, and dysthymic illness, and much less mania, hypomania, or psychotic illness compared to patients presenting initially in relatively pure mania.”

They conclude: “The findings support two markedly dissimilar subtypes of BD, and call for more explicit therapeutic studies of mixed-states.”

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

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In bipolar disorder patients with mania, those with mixed episodes, anxiety, or rapid cycling, as well as individuals at high risk for depression relapse, are more likely to receive antidepressants than other patients with the mood disorder, researchers have found.

“The primary goal of treatment of mania is to restore behavioral control as quickly as possible in order to minimize danger to self and others and to limit the high economic, social, and personal costs of manic episodes,” explain Eduard Vieta (University Clinic Hospital of Barcelona, Spain) and team.

They add that although guidelines recommend the discontinuation of antidepressant treatment during episodes of mania, as it may exacerbate symptoms, some bipolar patients with mania continue to receive such treatment.

To assess the prevalence of antidepressant use during episodes of mania, and factors associated with antidepressant use during mania, the researchers studied data on 3684 bipolar disorder patients with mania/mixed mania who participated in the 2-year EMBLEM (The European Mania in Bipolar Longitudinal Evaluation of Medication) study.

Overall, 345 (14%) of 2416 patients with mania who continued into the maintenance phase of the study were taking antidepressant medications at baseline. Most antidepressant prescriptions were for selective serotonin reuptake inhibitors or serotonin-norepinephrine reuptake inhibitors (74.1%).

Analysis revealed that patients with mixed episodes were 3.28 times more likely to be prescribed antidepressants than those with mania-only episodes, and patients with rapid cycling were 1.67 times more likely to be prescribed antidepressants than those without rapid cycling.

Furthermore, a greater number of previous depressive episodes and a higher anxiety score were associated with an increased likelihood of antidepressant treatment during mania compared with a lower number of previous depressive episodes and a lower anxiety score.

The researchers also found that patients who were prescribed antidepressants had significantly higher depression scores on the Clinical Global Impressions-Bipolar Disorder scale at both 12 weeks and 24 months than those who were not prescribed antidepressants, at scores of 2.11 and 2.02, versus 1.65 and 1.60, respectively.

Similarly, patients who were prescribed antidepressants had a higher depression relapse rate at 12 weeks and 24 months compared with other patients, at 26.6% and 31.3%, versus 15.6% and 19.3%, respectively.

Vieta and team summarize: “Patients with mania receiving antidepressants are more likely to be outpatients with mixed episodes, anxiety, or rapid cycling and have a higher risk of depression relapse during follow-up.”

They conclude: “These findings suggest that there is an unmet need to treat effectively the depressive burden within bipolar disorder, even during manic episodes, and that clinicians (regardless of whether they are right or wrong) use what they think might help, even against all the evidence.”

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

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