Two-Year Syndromal and Functional Recovery in 219 Cases of First-Episode Major Affective Disorder With Psychotic Features
Mauricio Tohen, M.D., Dr.P.H., John Hennen, Ph.D., Carlos M. Zarate, Jr., M.D., Ross J. Baldessarini, M.D., Stephen M. Strakowski, M.D., Andrew L. Stoll, M.D., Gianni L. Faedda, M.D., Trisha Suppes, M.D., Ph.D., Priscilla Gebre-Medhin, M.S., and Bruce M. Cohen, M.D., Ph.D.

OBJECTIVE: Psychotic affective disorders are the most prevalent idiopathic psychoses, but their outcome from onset has rarely been studied. In this study, the authors determined the rate and latency of syndromal recovery and rates of functional recovery after first lifetime hospitalization in patients with first-episode psychotic affective disorders. METHOD: From first lifetime hospitalization in 1989–1996, 219 patients with a DSM-IV psychotic affective illness were assessed at intervals over 24 months. Time to syndromal recovery (no longer meeting DSM-IV episode criteria) was assessed by survival analysis, and functional recovery (regaining baseline vocational and residential status) was rated. Factors associated with recovery were identified by bivariate and multivariate methods. RESULTS: By 3, 6, 12, and 24 months after first hospitalization, syndromal recovery was attained by 65.1%, 83.7%, 91.1%, and 97.5%, respectively, of subjects. Time to syndromal recovery (6.1 weeks to 50% of subjects recovered) was shorter for patients who had bipolar disorder, were married, were age 30 or older at onset, lacked comorbidity, required relatively brief hospitalization, and received fewer medicines. Functional recovery by 6 (30.4%) and 24 months (37.6% of patients) was 2.6–2.7 times less likely than syndromal recovery; 63.1% of those recovering syndromally did not recover functionally by 2 years. Functional recovery was associated with older age at onset and shorter hospitalization. Annual recovery rates remained stable as mean hospital length of stay decreased 3.6-fold over the 8-year study period. CONCLUSIONS: Syndromal recovery was attained by most psychotic affective disorder patients soon after hospitalization, but only one-third recovered functionally by 24 months. The findings suggest that these very common psychotic illnesses can carry a grave functional prognosis from the initial episode and first hospitalization.

Prognosis - Functional recovery is limited in people with bipolar disorder
Evidence Based Mental Health 2004;7:69

ORIGINAL ARTICLE
Tohen M, Zarate CA, Hennen J, et al. The McLean-Harvard first-episode mania study: prediction of recovery and first recurrence. Am J Psychiatry 2003;160:2099–107.
Question: What is the prognosis for people hospitalised with first episode bipolar disorder?



METHODS
Design: Prospective cohort study, part of the larger decade long McLean-Harvard First-Episode Project.

Setting: Inpatient units at McLean Division of Massachusetts General Hospital; 1989 to 1996.

Population: 173 people (mean age 33 years, 55% male) were consecutively recruited within 72 hours of psychiatric hospitalisation for manic (75%) or mixed (25%) episode bipolar disorder (DSM-IV criteria). Exclusions: current substance withdrawal, delirium, previous psychiatric hospitalisation unless for detoxification only, documented IQ <70, ill for >1 year, previous treatment with a mood stabiliser or antipsychotic for >3 months in total.

Prognostic factors: Participants were assessed weekly until discharge. Semistructured telephone interviews were conducted at 6, 12, 24, 26, and 48 months by experienced assessors. Information obtained included symptoms, occupational status, residential status, current treatment, and determination of syndromal, symptomatic, and functional recovery.

Outcomes: Likelihood of syndromal, symptomatic, and functional recovery (according to occupational and residential status); risks of first relapse or recurrence.

Follow up period: Average 4.86 years, 87% followed for >=2 years.



MAIN RESULTS
Syndromal recovery: 98% experienced syndromal recovery at 2 years. Predictors of earlier syndromal recovery were shorter initial hospitalisations (HR 1.99, 95% CI 1.36 to 2.93, p<0.001), female sex (HR 1.72, 95% CI 1.16 to 2.56, p = 0.008), and below median initial depression ratings (HR 1.65, 95% CI 1.14 to 2.39, p = 0.008). Symptomatic recovery: 72% had symptomatic recovery at 2 years. Functional recovery: at 2 years, 43% had functional recovery. Predictors of functional recovery were age >=30 years (OR 3.28, 95% CI 1.58 to 6.82, p = 0.006) and shorter initial hospitalisations (OR 2.82, 95% CI 1.36 to 5.88, p = 0.006). First relapse or recurrence: 20% had new episodes of mania, 20% new episodes of depression and 19% switched phases without recovery within 2 years (see http://www.ebmentalhealth.com/supplemental for table). Predictors of mania were initial mood-congruent psychotic features (HR 2.79, 95% CI 1.31 to 5.91, p = 0.05); low premorbid occupational status (HR 2.53, 95% CI 1.15 to 5.55, p = 0.02), and initial manic versus mixed state (HR 3.38, 95% CI 1.00 to 11.5 p = 0.05). Predictors of depression were higher premorbid occupational status (HR 5.08, 95% CI 2.16 to 11.90, p<0.0001); initial mixed presentation (HR 4.52, 95% CI 2.23 to 9.16, p<0.0001); and any comorbidity (HR 2.60, 95% CI 1.20 to 5.66 p = 0.02).



CONCLUSIONS
Among people with bipolar disorder who require hospitalisation, many have relapses, switches, and limited functional recovery.

Schizophrenia, Bipolar May Share Cause
Both Mental Illnesses Linked to Problem With Genes That Make Nerve Coating
By Salynn Boyles
WebMD Health News

Sept. 4, 2003 -- New research offers compelling evidence that the mental illnesses schizophrenia and bipolar disorder have a common genetic cause. The findings could eventually lead to better treatments for these and other diseases of the brain, researchers say.

The researchers used newly available, highly sensitive, molecular testing techniques to examine the postmortem brains of 15 people with schizophrenia, 15 people with bipolar disorder, and 15 people with neither illness. They found that the genes responsible for producing the protective coating around nerves in the brains of the people with the mental illnesses were less active than normal.

This protective coating around nerves -- called myelin -- insulates the nerves and aids the transmission of signals from the brain to the rest of the body.

Several previous studies have shown abnormalities in genes responsible for myelin production in the brains of people with schizophrenia, but this research is the first to identify similar abnormalities in the brains of people with bipolar disorder (previously called manic depression).

Researcher Sabine Bahn, MD, PhD, and colleagues from Cambridge, England's Babraham Institute found a high degree of overlap in gene activity between the brains of people with schizophrenia and bipolar disorder. Their findings are reported in the Sept. 5 issue of The Lancet.
Don't Blame Dopamine

Bahn tells WebMD that her research and the earlier myelin findings argue against the widely held theory that schizophrenia and similar disorders are caused by the brain's overproduction of the brain chemical dopamine.

"The dopamine hypothesis has been studied for the last 20 years, but nothing concrete has been proven," she says. "We are not saying that a myelin hypothesis should replace the dopamine hypothesis, but, rather, that we should all just take a step back and see what these new technologies tell us."

Mount Sinai School of Medicine psychiatry and biological chemistry Professor Kenneth L. Davis, MD, who led one of the first research teams to link underactive myelin genes to schizophrenia, says the research has prompted a sea change in the thinking about the cause of mental illness.

Schizophrenia is a disease that everyone thought was related to nerve cells and signal transmission, not myelin, he tells WebMD. Researchers now know that myelin genes are less active in schizophrenia and bipolar disorder. What they need to find out is what these genes do and why they are less active, he says.

The long-range hope, Davis says, is that answering these questions will eventually lead to better treatments for schizophrenia, bipolar disorder, and other mental illnesses.

"If we can figure out what these genes do and why they are [underactive] then maybe we can develop new targets for drug development," he says. "Right now there is no obvious drug target that comes from this work, but as this research evolves new targets could arise."

I know antidepressants made my condition worse. I will never take them again.

Abstract
Background

Antidepressants administered to bipolar subjects may induce manias, mixed states, or rapid cycling. More recently, we have noted that long-term use of antidepressants may induce a chronic dysphoric, irritable state.
Method

A case series is presented in which six type I bipolar subjects receiving antidepressants continuously for several years developed chronic irritable dysphoria.
Results

A triad of dysphoric mood, irritability, and middle insomnia that is frequently associated with occupational and social dysfunction can occur in some bipolar patients receiving antidepressants for at least 3 years. Typically, initial treatments with antidepressants for the index episode were effective. Over time, depressive symptoms returned and would transiently improve with dose increase or change of agents. Ultimately, the dysphoria and associated symptoms became chronic and resulted in dysfunction. Concomitant mood stabilizer did not appear to alter this pattern. Discontinuation of antidepressants was associated with a slow and gradual improvement in these symptoms over the ensuing year.
Conclusion

Additional studies are required to investigate safety of long-term use of antidepressants in bipolar illness.

Bipolar linked with impairment of social functioning

August 1, 2008, SAO PAULO, Brazil—Even when they’re not suffering from mania or depressive symptoms—known as being in a euthymic state—people with bipolar disorder appear to have a more difficult time in social situations, research has found.

Brazilian researchers studied people with bipolar I disorder with respect to conversational skills, social self-confidence, and openness to new people and situations, compared to people without the disorder.

They found that those with bipolar in a euthymic state displayed inhibited or over-attentive behavior in relation to other people and their environment. Researchers said this might have a negative impact on their level of social functioning and quality of life.

The study, from the Australian and New Zealand Journal of Psychiatry, was titled “Social dysfunction in bipolar disorder: Pilot study.”