A Pilot Study of Antidepressant-Induced Mania in Pediatric Bipolar Disorder: Characteristics, Risk Factors, and the Serotonin Transporter Gene Effects of recurrence on the cognitive performance of patients with bipolar I disorder: implications for relapse prevention and treatment adherence. Antidepressant-associated switches from depression to mania in severe bipolar disorder. Impact of substance use disorders on recovery from episodes of depression in bipolar disorder patients: prospective data from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). Antidepressants in Type II Versus Type I Bipolar Depression: A Randomized Discontinuation Trial Interpersonal and social rhythm therapy for adolescents with bipolar disorder: treatment development and results from an open trial A Consecutive Series of Treated Affected Offspring of Parents with Bipolar Disorder: Is Response Associated with the Clinical Profile? Efficacy and Safety of Risperidone and Quetiapine in Adolescents With Bipolar II Disorder Comorbid With Conduct Disorder A one-year open-label trial of risperidone augmentation in lithium nonresponder youth with preschool-onset bipolar disorder. Mood episodes and mood disorders: patterns of incidence and conversion in the first three decades of life. The prevalence of major depressive and bipolar disorders in Hungary. Results from a national epidemiologic survey. Predictors of recurrence in bipolar disorder: primary outcomes from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). The prospective course of rapid-cycling bipolar disorder: findings from the STEP-BD. Number needed to treat analyses of drugs used for maintenance treatment of bipolar disorder Bipolar outcome in the course of depressive illness. Phenomenologic, familial, and pharmacologic predictors. Patterns of pharmacological maintenance treatment in a community mental health services bipolar disorder cohort study (SIN-DEPRES). Four-year prospective outcome and natural history of mania in children with a prepubertal and early adolescent bipolar disorder phenotype. In major affective disorders, early life trauma predict increased nitro-oxidative stress, lipid peroxidation and protein oxidation and recurrence of major affective disorders, suicidal behaviors and a lowered quality of life A preliminary functional magnetic resonance imaging study of prefrontal-amygdalar activation changes in adolescents with bipolar depression treated with lamotrigine. Bupropion as an Add-on Therapy in Depressed Bipolar Disorder Type I Patients With Comorbid Cocaine Dependence Reduced mania and depression in juvenile bipolar disorder associated with long-chain ω-3 polyunsaturated fatty acid supplementation Course and outcome following a first episode of mania: four-year prospective data from the Systematic Treatment Optimization Program (STOP-EM). Course sequences in bipolar disorder: depressions preceding or following manias or hypomanias.
BACKGROUND Antidepressant-induced mania ( AIM ) has been described in bipolar disorder ( BD ) and has been associated with the short-allele of the serotonin transporter gene ( 5-HTT ) . We wished to investigate the frequency of and risk factors for AIM in pediatric patients with or at high risk for BD . METHODS Fifty-two children and adolescents ( 30 with BD and 22 with subthreshold manic symptoms , 15.1 + /- 3.4 years old ) , all with a parent with BD , were interviewed with their parents for manic/depressive symptoms occurring before and after past antidepressant treatment .  The 47 subjects with serotonin reuptake inhibitor ( SSRI ) exposure  were genotyped for the 5-HTT polymorphism . RESULTS Fifty percent of subjects were AIM + and 25.5 % had new onset of suicidal ideation . The AIM + and AIM - groups did not differ significantly in relation to allele ( p = .36 ) or genotype ( p = .53 ) frequencies of the 5-HTT polymorphism . The AIM + subjects were more likely to have more comorbidities ( 3.2 vs. 2.4 ; p = .02 ) and be BD type I ( p = .04 ) than AIM - subjects . CONCLUSIONS Youth with or at high risk for BD may be particularly vulnerable to SSRI AIM and thus should be monitored if given SSRIs . In this preliminary study , we did not find that the 5-HTT polymorphism significantly influenced vulnerability to AIM OBJECTIVE To determine if the repeated occurrence of manic episodes in bipolar I disorder ( BD-I ) patients is associated with reduced cognitive performance , which could in turn imply a worsening in the disorder 's evolution . METHOD Cognitive performance in euthymic patients was assessed using  attention , memory , and executive function tests  on 24 BD-I patients who had experienced only 1 manic episode , on 27 BD-I patients with 2 manic episodes , on 47 BD-I patients with 3 or more manic episodes , and on 66 healthy control subjects . RESULTS In BD-I patients , number of manic episodes was positively associated with poorer performance on neurocognitive tests , an association that was not accounted for by depression , disease chronicity , onset , or medication . Significant differences in attention and executive function were found between patients and controls and in those patients who had had just 1 manic episode compared to those who had 3 or more . CONCLUSION The number of manic episodes predicted poor cognitive performance , suggesting that the recurrence of mania may have a long-term neuropsychological impact . Prospect i ve follow-up studies need to be completed to explore this effect further as better treatment adherence may have a protective effect on neurocognitive function OBJECTIVES To determine whether switching from depression to mania is part of the natural history of bipolar illness or results from antidepressant ( AD ) treatment by examining bipolar patients with psychosis early in their illness course . METHODS A multi-facility cohort of 123 first-admission in patients , aged 15 - 60 years , with DSM-IV bipolar disorder ( BD ) with psychotic features , was followed for four years , and 76 individuals experienced at least one episode of depression .  Frequency of and risk factors for switches from depression to mania , time to switch , and duration of the subsequent manic episode were examined in relation to AD use ( with anti-manic and /or antipsychotic medications ) . RESULTS The 76 respondents experienced 113 depressive episodes . Those prescribed ADs had more depressive episodes and spent more time depressed than non-users . A total of 23 depressive episodes in 17 respondents ended in a manic/hypomanic/mixed episode ( 20 % ) . The time to switch and duration of the subsequent manic episode were not significantly different for the seven respondents and nine episodes involving AD treatment versus the 10 respondents and 14 episodes without ADs . None of the risk factors ( age of onset < or=18 years , childhood psychopathology , depressive first episode , substance abuse at index admission , bipolar family history , type of AD used ) was associated with switching . CONCLUSIONS In this sample with severe BD , switching from depression to mania was not associated with AD treatment . Respondents who experienced switching appeared to have a more relentless form of BD . In only a few did ADs appear to be responsible for the switch OBJECTIVE Bipolar disorder is highly comorbid with substance use disorders , and this comorbidity may be associated with a more severe course of illness , but the impact of comorbid substance abuse on recovery from major depressive episodes in these patients has not been adequately examined . The authors hypothesized that comorbid drug and alcohol use disorders would be associated with longer time to recovery in patients with bipolar disorder . METHOD Subjects ( N=3,750 ) with bipolar I or bipolar II disorder enrolled in the Systematic Treatment Enhancement Program for Bipolar Disorder ( STEP-BD ) were followed prospect ively for up to 2 years . Prospect ively observed depressive episodes were identified for this analysis . Subjects with a past or current drug or alcohol use disorder were compared with those with no history of drug or alcohol use disorders on time to recovery from depression and time until switch to a manic , hypomanic , or mixed episode . RESULTS During follow up , 2,154 subjects developed a new-onset major depressive episode ; of these , 457 subjects switched to a manic , hypomanic , or mixed episode prior to recovery . Past or current substance use disorder did not predict time to recovery from a depressive episode relative to no substance use comorbidity . However , those with current or past substance use disorder were more likely to experience switch from depression directly to a manic , hypomanic , or mixed state . CONCLUSIONS Current or past substance use disorders were not associated with longer time to recovery from depression but may contribute to greater risk of switch into manic , mixed , or hypomanic states . The mechanism conferring this increased risk merits further study Background We sought to test the hypothesis that antidepressants ( ADs ) may show preferential efficacy and safety among patients with type II bipolar disorder ( BD , BD-II ) more than patients with type I BD ( BD-I ) . Methods Patients with Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition , BD-I ( n = 21 ) and BD-II ( n = 49 ) in acute major depressive episodes were treated with ADs plus mood stabilizers to euthymia sustained for 2 months and then r and omized openly to continue or discontinue ADs for up to 3 years . Outcomes were episode recurrences and changes in st and ardized symptom ratings . Results In follow-up averaging 1.64 years , both subgroups showed improvement in depressive episode frequency with AD continuation , but contrary to the hypothesis , more improvement was seen in BD-I than in BD-II ( for type II , mean [ st and ard deviation ] decrease in depressive episodes per year , 0.21 [ 0.26 ] ; for type I , mean ( SD ) decrease , 0.35 [ 0.15 ] ) . Subjects with BD-II who continued on ADs had slightly more depressive , but fewer manic/hypomanic , episodes than subjects with BD-I. No notable differences were seen in either group in time to a recurrence of mood episodes or total time-in-remission . Conclusions The findings do not confirm the hypothesis that long-term AD treatment in patients with BP-II has better outcomes than in patients with BD-I , except somewhat lower risk of manic/hypomanic episodes Background : In adolescents and adults , bipolar disorder ( BD ) is associated with significant morbidity , mortality , and impairment in psychosocial and occupational functioning . IPSRT is an empirically supported adjunctive psychotherapy for adults with bipolar disorder , which has been shown to help delay relapse , speed recovery from a bipolar depressive episode , and increase occupational and psychosocial functioning in adults with BD . This study is design ed to describe the adolescent‐specific developmental adaptations made to IPSRT ( i.e. , IPSRT‐A ) and to report the results from an open trial of IPSRT‐A with 12 adolescents with a bipolar spectrum disorder . Method : Interpersonal and Social Rhythm Therapy was adapted to be developmentally relevant to adolescents with bipolar disorder . Twelve adolescents ( mean age 16.5±1.3 years ) diagnosed with a bipolar spectrum disorder participated in 16–18 sessions of adjunctive IPSRT‐A over 20 weeks . Manic , depressive , and general symptoms and global functioning were measured at baseline , monthly during treatment , and at post‐treatment . Adolescent satisfaction with treatment was also measured . Results : Feasibility and acceptability  of IPSRT‐A were high ; 11/12 participants completed treatment , 97 % of sessions were attended , and adolescent‐rated satisfaction scores were high . IPSRT‐A participants experienced significant decreases in manic , depressive , and general psychiatric symptoms over the 20 weeks of treatment . Participants ' global functioning increased significantly as well . Effect sizes ranged from medium‐large to large . Conclusions : IPSRT‐A appears to be a promising adjunctive treatment for adolescents with bipolar disorder . A current r and omized controlled trial is underway to examine effects of adjunctive IPSRT‐A  on psychiatric symptoms and psychosocial functioning . Depression and Anxiety , 2010 . © 2010 Wiley‐Liss , Objective : In adults with established bipolar disorder ( BD ) , differential response to  mood stabilizers  has been associated with the clinical profile . Long-term treatment studies of youth with BD are lacking . This paper provides longitudinal observations of response to  mood stabilizers  early in the course of illness in youth with BD . Method : We report on 15 research patients who , as adolescents , met DSM-IV lifetime criteria for a bipolar spectrum disorder and required long-term treatment . These youths derived from families with one parent having BD whose course and long-term treatment response were determined in accordance with research criteria . The patients were offered lithium , and if they failed to respond or refused it , they were treated with either an anticonvulsant or an atypical antipsychotic . Using a vali date d scale , an independent rater retrospectively blindly scored the response to long-term treatment . Results : Those patients who stabilized on  lithium  derived from lithium-responsive families , whereas those who stabilized on an  antipsychotic  derived from lithium-nonresponsive families . The clinical course in the youths stabilized by lithium differed from that in the youths stabilized by an atypical antipsychotic . Conclusions : Our findings suggest that the clinical profile may help in selecting effective stabilizing treatment and that a proportion of youth can be stabilized on monotherapy . This is a small case series with nonr and om treatment assignment , and the findings should be considered tentative Abstract Although a frequent co-occurrence between bipolar disorder ( BD ) and conduct disorder ( CD ) in youth has been frequently reported , data about pharmacological management are scarce and focused on BD type I. Second generation antipsychotics are frequently used in clinical practice , but no comparative studies are available . The aim of this exploratory study was to compare efficacy and safety of risperidone and quetiapine in a sample of adolescents presenting a BD type II comorbid with CD . Twenty-two patients diagnosed with a structured interview according to Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition , ( male/female ratio , 12/10 ; mean ( SD ) age 15.0 ( 1.4 ) years ) were r and omized in 2 treatment groups  ( quetiapine [ n = 12 ] vs risperidone [ n = 10 ] ) , treated with flexible doses , and followed up for 12 weeks . Efficacy measures assessed manic symptoms , aggression , anxiety , depression , global clinical severity , and impairment . Safety measures included body mass index , serum prolactin , extrapyramidal adverse effects , and electrocardiogram . At the end of the study , all patients improved in all efficacy measures . Both treatments showed similar efficacy in reducing manic symptoms and aggression . Quetiapine was more effective in improving anxiety and depressive symptoms . A change in body mass index was found , and in a post hoc analysis , it was significant only in the risperidone group . Prolactin significantly increased only in the risperidone group . In BD type II , CD comorbidity , quetiapine , or risperidone monotherapy may be effective and relatively safe , although the small sample size , the limited duration of the study , and the design ( lack of a blind assessment s and of a placebo group ) make it difficult to draw definitive conclusions OBJECTIVE The aim of this study was to assess the safety and efficacy of risperidone augmentation of lithium in preschool-onset bipolar disorder ( BD ) among youth who insufficiently respond to lithium monotherapy .  METHOD Thirty-eight subjects between the ages of 4 and 17 years ( mean age = 11.37 + /- 3.8 years ) with onset of BD in preschool years ( manic or mixed episode ) entered this 12-month trial . All subjects received lithium monotherapy . Patients who failed to adequately respond to lithium monotherapy after 8 weeks and those who relapsed after an initial response were given risperidone augmentation for up to 11 months . The Young Mania Rating Scale ( YMRS ) was the primary outcome measure . Response was defined as a > or = 50 % decrease from baseline . Additional data were collected on diagnostic comorbidity , family history , number of hospitalizations , perinatal risk factors , history of physical or sexual abuse , Child Depression Rating Scale-Revised ( CDRS-R ) , Clinical Global Impression ( CGI ) scale for BD ( CGI-BP ) , Children 's Global Assessment Scale ( C-GAS ) , and adverse medication effects . RESULTS Of the 38 subjects treated with lithium monotherapy , 17 responded , whereas 21 required augmentation with risperidone .  Response rate in the youths treated with lithium + risperidone was 85.7 % ( n = 18/21 ) . Significant predictors of inadequate response to lithium monotherapy requiring augmentation were : ( 1 ) attention-deficit/hyperactivity disorder ( ADHD ) , ( 2 ) severity at baseline , ( 3 ) history of sexual or physical abuse , and ( 4 ) preschool age . Combination treatment of lithium and risperidone was found to be safe and well tolerated . CONCLUSIONS A substantial proportion of youth with a history of preschool-onset BD treated with lithium  were either nonresponders or partial responders . Subsequent augmentation of lithium with risperidone in these cases was well tolerated and efficacious . Potential predictors of lithium nonresponse identified in this study may guide the choice of medications earlier in the treatment process OBJECTIVES Significant questions remain regarding both the incidence patterns of mood episodes in adolescents and young adults from the community and the conversion rate from unipolar to bipolar disorders . We addressed these issues by examining data from a prospect i ve longitudinal community study to ( i ) determine the cumulative incidence of mood episodes and disorders in the first three decades of life ; ( ii ) determine the risk for first onset of depression among individuals with a previous history of hypomanic/manic episodes and vice versa ; and ( iii ) determine the clinical and treatment characteristics of these subjects . METHODS Using the Munich-Composite International Diagnostic Interview , clinical ly trained interviewers assessed mood episodes and mental disorders in 3,021 community subjects ( aged 14 - 24 at baseline and 21 - 34 at third follow-up ) . RESULTS The estimated cumulative incidence at age 33 was 2.9 % for manic , 4.0 % for hypomanic , 29.4 % for major depressive , and 19.0 % for minor depressive episodes ; overall , 26.0 % had unipolar major depression , 4.0 % bipolar depression , 1.5 % unipolar mania , and 3.6 % unipolar hypomania ( no major depression ) . Overall , 0.6 % and 1.8 % had unipolar mania or hypomania , respectively , without indication for even minor depression . A total of 3.6 % of the initial unipolar major depression cases subsequently developed (hypo)mania , with particularly high rates in adolescent onset depression ( < 17 years : 9 % ) . A total of 49.6 % of the initial unipolar mania cases subsequently developed major depression and 75.6 % major or minor depression . While bipolar cases had more adverse clinical and course depression characteristics and higher treatment rates than unipolar depressed cases , bipolar cases did not significantly differ in mania characteristics from unipolar mania cases . CONCLUSIONS Unipolar and bipolar mood disorders are more frequent than previously thought in adolescence and young adulthood , a time period when both the recognition and the intervention rates by the healthcare system are rather low . ' Conversion ' to bipolar disorder is limited in initial unipolar depression , but common in initial unipolar mania . The remaining unipolar mania cases appear to be significant in terms of clinical and course characteristics and thus require more research attention to replicate these findings In order to estimate the prevalence of affective disorders in Hungary a sample of the Hungarian adult population ( 18 - 64 years ) selected at r and om was interviewed using the Diagnostic Interview Schedule ( DIS ) which generated DSM-III-R diagnoses . The lifetime rate for Major Depressive Disorder ( MDD ) was 15.1 % , and for Bipolar Disorders ( BD ) 5.1 % . The female-to-male ratio was 2.7 for MDD and nearly equal for BD . The 1-year and 1-month period prevalence rates were 7.1 % and 2.6 % for MDD and 0.9 % and 0.5 % for manic episodes . A higher rate of divorced or separated persons was found among individuals with a lifetime diagnosis of MDD . Besides these , the lifetime diagnosis of BD coexisted with higher rates of the never-married state . The highest hazard rate for the development of BD or MDD was in the range 15 - 19 years but in MDD another peak was also found in the range 45 - 50 years . The first peak was characteristic of the recurrent , and the other one of the single form of MDD . Insomnia , loss of energy , decreased interest , concentration problems were the most common symptoms during the depressive episode , independent of polarity . Higher rates of lifetime diagnosis of dysthymia and all kinds of anxiety disorder were revealed among persons with MDD . BD was associated with GAD ( Generalized Anxiety Disorder ) , and panic disorder more often than chance OBJECTIVE Little is known about clinical features associated with the risk of recurrence in patients with bipolar disorder receiving treatment according to contemporary practice guidelines . The authors looked for the features associated with risk of recurrence . METHOD The authors examined prospect i ve data from a cohort of patients with bipolar disorder participating in the multicenter Systematic Treatment Enhancement Program for Bipolar Disorder ( STEP-BD ) study for up to 24 months . For those who were symptomatic at study entry but subsequently achieved recovery , time to recurrence of mania , hypomania , mixed state , or a depressive episode was examined with Cox regression . RESULTS Of 1,469 participants symptomatic at study entry , 858 ( 58.4 % ) subsequently achieved recovery . During up to 2 years of follow-up , 416 ( 48.5 % ) of these individuals experienced recurrences , with more than twice as many developing depressive episodes ( 298 , 34.7 % ) as those who developed manic , hypomanic , or mixed episodes ( 118 , 13.8 % ) . The time until 25 % of the individuals experienced a depressive episode was 21.4 weeks and until 25 % experienced a manic/hypomanic/mixed episode was 85.0 weeks . Residual depressive or manic symptoms at recovery and proportion of days depressed or anxious in the preceding year were significantly associated with shorter time to depressive recurrence . Residual manic symptoms at recovery and proportion of days of elevated mood in the preceding year were significantly associated with shorter time to manic , hypomanic , or mixed episode recurrence . CONCLUSIONS Recurrence was frequent and associated with the presence of residual mood symptoms at initial recovery . Targeting residual symptoms in maintenance treatment may represent an opportunity to reduce risk of recurrence OBJECTIVE In a naturalistic follow-up of adult bipolar patients , the authors examined the contributions of demographic , phenomenological , and clinical variables , including antidepressant use , to prospect ively observed mood episode frequency . METHOD For 1,742 bipolar I and II patients in the Systematic Treatment Enhancement Program for Bipolar Disorder ( STEP-BD ) , episodes of mood disorders were evaluated for up to 1 year of treatment . RESULTS At entry , 32 % of the patients met the DSM-IV criteria for rapid cycling in the pre study year . Of the 1,742 patients , 551 ( 32 % ) did not complete 1 year of treatment . Among the 1,191 patients remaining , those with prior rapid cycling ( N=356 ) were more likely to have further recurrences , although not necessarily more than four episodes per year . At the end of 12 months , only 5 % ( N=58 ) of the patients could be classified as rapid cyclers ; 34 % ( N=409 ) had no further mood episodes , 34 % ( N=402 ) experienced one episode , and 27 % ( N=322 ) had two or three episodes . Patients who entered the study with earlier illness onset and greater severity were more likely to have one or more episodes in the prospect i ve study year . Antidepressant use during follow-up was associated with more frequent mood episodes . CONCLUSIONS While DSM-IV rapid cycling was prospect ively observed in only a small percentage of patients , the majority of these patients had continued recurrences at lower but clinical ly significant rates . This suggests that cycling is on a continuum and that prevention of recurrences may require early intervention and restricted use of antidepressants Rationale Due to the episodic and chronic nature of bipolar disorder ( BD ) , maintenance therapy represents a critical part of treatment ; however , there is a paucity of studies comparing effectiveness of available long-term treatments . Objective The aim of this study is to determine and compare the efficacy of pharmacological treatments for maintenance treatment of BD by means of the number needed to treat ( NNT ) . Methods The efficacy of drugs used for maintenance treatment of BD , as emerging from the results of r and omized controlled trials , was assessed using the size effect measure of NNT . PubMed search es were conducted on English- language articles published until May 2010 using the search terms “ bipolar disorder , ” “ mania , ” “ mixed episode , ” or “ bipolar depression , ” cross-referenced with trial characteristic search phrases and generic names of medications . The search was supplemented by manually review ing reference lists from identified publications . Results In 15 studies , aripiprazole , olanzapine , quetiapine , risperidone long-acting injection , lithium , lamotrigine , and divalproex proved effectiveness in terms of NNTs ( ≥10 % advantage over placebo ) for prevention of relapse into any mood episode . Quetiapine , lithium , risperidone long-acting injection , aripiprazole , and olanzapine are effective in manic recurrence prevention .  Lamotrigine , quetiapine , and lithium present significant NNTs for prevention of depressive relapses . Conclusions All of the pharmacological agents assessed were effective in the prevention of any kind of mood episode ; however , different efficacy profiles were found for prevention of manic and /or depressive relapses . The comparison of NNT values of the available agents may represent a useful tool in clinical setting s , in order to facilitate implementation of long-term pharmacological interventions in patients with BD Twenty percent of a cohort of 206 outpatient depressives with no past bipolar history switched during prospect i ve observation . These 41 prob and s developed manic periods on the average of 6.4 years ( median 4 , range 1 - 25 ) after their first depressive episode . The change in polarity occurred throughout the life span , but was most common in adolescence and early adulthood . The following variables were found useful in predicting this outcome : onset less than or equal to 25 years , bipolar family history , loaded pedigrees , precipitation by childbirth , hypersomnic-retarded phenomenology , and pharmacologically-mobilized hypomania . Although the respective sensitivities of these findings were relatively low ( 32 - 71 % ) , their specificities ranged from 69 % to 100 % for bipolar outcome ; the diagnostic specificity of any 3 of these variables when combined was 98 % . When compared with nonbipolar depression , bipolar disorder was seldom chronologically secondary to nonaffective psychiatric disorders . These findings suggest that many young depressives with lethargy and oversleeping are not manifesting a " neurotic " disorder , but rather a precursor of primary bipolar affective disorder . Finally , a psychotically depressed adolescent or young adult with positive bipolar family history should be observed for eventual bipolar outcome , especially when the clinical presentation is that of stupor Maintenance therapy in bipolar disorder ( BD ) is usually required to prevent relapses and improve residual symptoms . Therefore , in this study , we describe patterns of pharmacological maintenance treatment and identify associated clinical features . This prospect i ve multicentre epidemiological study recruited a cohort of 739 consecutive out- patients with clinical ly stable BD . Clinical stability was assessed at baseline with the Clinical Global Impression scale for BD and depressive symptoms with the Hamilton Depression Rating Scale .  Psychotropic medications were classified and analysed according to their mechanism as well as use . Logistic regression models were used to examine the associations between pharmacological strategies and clinical features . Longer time since last episode [ odds ratio ( OR ) 1.002 , p < 0.0001 ] and family history of psychiatric disorders ( OR 1.911 , p = 0.028 ) were associated with lithium in monotherapy ;  manic polarity of the most recent episode ( OR 3.300 , p = 0.006 ) and longer duration of clinical stability ( OR 1.009 , p = 0.034 ) with antipsychotic in monotherapy ;  depressive polarity of the most recent episode ( OR 2.567 , p = 0.003 ) and bipolar II disorder diagnosis ( OR 2.278 , p = 0.008 ) with antidepressant combination ;  no ongoing psychiatric co-morbidity ( OR 0.230 , p = 0.004 ) with lithium and anticonvulsant ;  manic polarity of the most recent episode ( OR 3.774 , p < 0.0001 ) with lithium and antipsychotic ;  manic polarity of the most recent episode ( OR 2.907 , p = 0.028 ) with lithium , anticonvulsant and antipsychotic . The pharmacological patterns followed published recommendations , except for the excessive use of antidepressants . This study reveals clinical factors closely related to prescription patterns BACKGROUND Diagnosis of child mania has been contentious . OBJECTIVE To investigate natural history and prospect i ve validation of the existence and long-episode duration of mania in children . DESIGN Four-year prospect i ve longitudinal study of 86 subjects with intake episode mania who were all assessed at 6 , 12 , 18 , 24 , 36 , and 48 months . The phenotype was defined as DSM-IV bipolar I disorder ( manic or mixed ) with at least 1 cardinal symptom ( elation and /or gr and iosity ) to ensure differentiation from attention-deficit/hyperactivity disorder . Parent and child informants were separately interviewed , by highly experienced research nurses , using the Washington University in St Louis Kiddie Schedule for Affective Disorders and Schizophrenia ( WASH-U-KSADS ) . A Children 's Global Assessment Scale score of 60 or less was needed to establish definite impairment . Treatment was by subjects ' community practitioners . SETTING Research unit in a university medical school . PARTICIPANTS Subjects were obtained from psychiatric and pediatric sites by consecutive new case ascertainment , and their baseline age was 10.8 + /- 2.7 years . Onset of the baseline episode  was 7.4 + /- 3.5 years . ( Data are given as mean + /- SD . ) MAIN OUTCOME MEASURES Episode duration , weeks ill , recovery/relapse rates , and outcome predictors . RESULTS Prospect i ve episode duration of manic diagnoses , using onset of mania as baseline date , was 79.2 + /- 66.7 consecutive weeks . Any bipolar disorder diagnosis occurred during 67.1 % + /- 28.5 % of total weeks , during the 209.4 + /- 3.3 weeks of follow-up . Subjects spent 56.9 % + /- 28.8 % of total weeks with mania or hypomania ( unipolar or mixed ) , and 38.7 % + /- 28.8 % of these were with mania . Major or minor depression and dysthymia ( unipolar or mixed ) occurred during 47.1 % + /- 30.4 % of total weeks . Polarity switches occurred 1.1 + /- 0.7 times per year . Low maternal warmth predicted faster relapse after recovery from mania ( chi(2 ) = 13.6 , P = .0002 ) , and psychosis predicted more weeks ill with mania or hypomania ( F(1,80 ) = 12.2 , P = .0008 ) . Pubertal status and sex were not predictive . ( Data are given as mean + /- SD . ) CONCLUSIONS These findings vali date the existence , long-episode duration , and chronicity of child mania . Differences from the natural history of adult bipolar disorder are discussed Early life trauma ( ELT ) may increase the risk towards bipolar disorder ( BD ) and major depression ( MDD ) , disorders associated with activated neuro-oxidative and neuro-nitrosative stress ( O&NS ) pathways . It has remained elusive whether ELTs are associated with O&NS and which ELTs are associated with distinct affective disorder phenotypes . This case-control study examined patients with BD ( n = 68 ) and MDD ( n = 37 ) and healthy controls ( n = 66 ) . The Child Trauma Question naire ( CTQ ) was used to assess specific ELT . We measured malondialdehyde ( MDA ) , lipid hydroperoxides ( LOOH ) , superoxide dismutase ( SOD ) , catalase , advanced oxidation protein products ( AOPP ) ; NO metabolites ( NOx ) , paraoxonase 1 activity , zinc , albumin , high density lipoprotein cholesterol and -SH groups and computed z-unit weighted composite scores . Physical neglect significantly predicts higher z-unit weighted composite scores of LOOH+SOD , LOOH+SOD+NOx , LOOH+SOD+NOx + MDA and LOOH+SOD+NOx + AOPP . Sexual abuse was associated with a significantly lower composite score of zinc+albumin+SH . Emotional abuse was associated with severity of depression and anxiety , number of depressive and manic episodes , alcohol and hypnotics use , lifetime suicidal behavior and lowered quality of life . Sexual abuse was associated with an increased risk towards BD , but not MDD . ELT , especially physical neglect , may drive increased (nitro-)oxidative stress coupled with lipid and protein oxidation , which - together with emotional abuse - may play a role in severity of illness , lowered quality of life and MDD . ELTs are also associated with the onset of BD , but this link did not appear to be related to activated O&NS pathways . These novel findings deserve confirmation in prospect i ve studies OBJECTIVES Hypotheses regarding mood dysregulation in bipolar disorder ( BD ) have centered on limbic overactivity with relative prefrontal underactivity during mood episodes . Therefore , we hypothesized that adolescents with bipolar depression successfully treated with lamotrigine would show decreases in amygdalar activation , and increases in prefrontal activation . METHODS Eight adolescents with BD underwent  functional magnetic resonance imaging ( fMRI ) at baseline and after eight weeks of lamotrigine treatment .  Blocks of negatively and neutrally valenced emotional pictures were presented during scanning , and subjects were asked to rate how each picture made them feel . Activation in bilateral amygdalae and dorsolateral prefrontal cortices ( DLPFC ) for negative minus neutral pictures was correlated with Children 's Depression Rating Scale ( CDRS ) scores . RESULTS Mean ( SD ) CDRS scores decreased significantly , from 53.0 ( 10.6 ) at baseline to 26.3 ( 5.3 ) at Week 8 . This clinical improvement was correlated with decreased right amygdalar activation ( r = 0.91 , p = 0.002 ) . At Week 8 , but not baseline , CDRS score was positively correlated with bilateral amygdalar activation ( r = 0.85 , p = 0.007 ) . DLPFC activation was not correlated with change in CDRS score . CONCLUSIONS These preliminary results indicate that adolescents with BD treated with lamotrigine demonstrated less amygdalar activation when viewing negative stimuli as depressive symptoms improved . Larger controlled studies are needed to confirm these findings Objectives The treatment of bipolar disorder type I ( BD-I ) with a comorbid cocaine dependence disorder ( CDD ) is a challenge in current psychiatric practice . Drugs with proven efficacy in manic/mixed episodes , such as atypical antipsychotics and mood stabilizers , sometimes do not prevent depressive relapses ; on the other h and , the use of antidepressants during acute depressive episodes may increase the risk of a manic switch . The aim of the present study was to investigate the short-term efficacy of bupropion augmentation in acutely depressed BD-I patients with co-occurring CDD . Methods Twelve depressed BD-I patients , with a comorbid CDD , treated with valproate 1000 to 1500 mg/d and aripiprazole 10 mg/d , were r and omly assigned to receive bupropion 150 mg/d as an open-label add-on therapy ( n = 5 ) or to continue their previous treatment ( n = 7 ) . Results After 4 weeks of observation , patients receiving add-on therapy with bupropion have improved in terms of Hamilton Depression Rating Scale scores and Drug Abuse Screening Test scores , with respect to those of the comparison group , whereas no significant increase of Young Mania Rating Scale scores over time was observed . Conclusions Our preliminary findings suggest that combining bupropion with mood stabilizers and atypical antipsychotics may be a good therapeutic option in short-term treatment of depressed BD-I patients with comorbid CDD Long-chain ω-3 polyunsaturated fatty acid ( LCn-3PUFA ) supplementation may improve symptoms of depression in children and bipolar disorder ( BD ) in adults . No studies have examined the effectiveness of LCn-3PUFA supplementation in the treatment of mania and depression in juvenile BD ( JBD ) when given as an adjunct to st and ard pharmacological treatment . Eighteen children and adolescents with JBD received supplements containing 360 mg per day eicosapentaenoic acid ( EPA ) and 1560 mg per day docosahexaenoic acid ( DHA ) for 6 weeks in an open-label study . Intake and fasting red blood cell ( RBC ) LCn-3PUFA , mania , depression and global function were assessed before and after supplementation . RBC EPA and DHA were significantly higher following supplementation . Clinician ratings of mania and depression were significantly lower and global functioning significantly higher after supplementation . Parent ratings of internalizing and externalizing behaviours were also significantly lower following supplementation . A larger r and omized controlled trial appears warranted in this participant population BACKGROUND First episode mania ( FEM ) cohorts provide an opportunity to identify windows for intervention to potentially alter the course of bipolar disorder ( BD ) . Despite several efforts to prospect ively characterize first episode patients , follow-up of such cohorts has seldom exceeded 1 year . We present 4-year outcomes from the STOP-EM FEM cohort . METHOD Of 101 identified FEM patients , 81 had longitudinal follow-up . Clinical evaluations including substance misuse , sociodemographics and family history were characterized using semi-structured instruments . Clinical re assessment s occurred every 6 months . RESULTS Within one year , all patients had remitted and 95 % recovered . Recurrence following remission occurred in 58 % of patients by 1 year and 74 % by 4 years ( 60 % depressive , 28 % manic and 12 % hypomanic ) . Recurrence within one year was associated with a higher rate of recurrence thereafter . Older age was associated with a shorter time to remission . Substance misuse was associated with delayed recovery and earlier recurrence . LIMITATIONS This prospect i ve multiwave longitudinal design employed may be limited by the assessment schedule and associated recall bias . The influences of attrition of this sample should be considered when attempting to generalize our findings . CONCLUSIONS Best practice s in FEM result in remission and recovery . While recurrence is common , minimizing recurrence within the first year through risk factor modification may alter the course of the BD BACKGROUND Inferior response to lithium treatment  has been reported in bipolar disorder ( BD ) patients with mania or hypomania following episodes of major depression ( DMI ) versus preceding depression ( MDI ) , with intervening euthymic periods . However , additional characteristics of BD course-patterns require further assessment . METHODS We review ed computerized clinical records and life-charts of 855 DSM-IV-TR BD-I or -II patients assessed and followed at mood-disorder centers in Cagliari or Rome to characterize their predominant course-sequences . RESULTS Morbidity over an average of 9.5 cycles in 18 years was characterized for sequencing of illness-episodes and euthymic intervals . Prevalent sequences included : major depression-hypomania ( 15.0 % ) , mania-major depression ( 14.6 % ) , major depression-mania ( 11.6 % ) , and rapid-cycling ( 9.6 % ) . Among subjects grouped by course-sequences ( based on mania , mixed-states , or hypomania and major or minor depression ) , depression-before-[hypo]mania ( DMI ) cases were more likely to be women , diagnosed BD-II , have first-episodes of depressive or anxiety disorder , spend more time ill in depression , and benefit less with long-term mood-stabilizing treatments than with the opposite pattern ( MDI ) . MDI patients were more likely to have substance-abuse and receive long-term mood-stabilizer treatments . Meta- analysis of 5 previous reports plus present findings found inferior treatment-response in DMI vs. MDI cases at a pooled risk-difference of 29 % [ CI : 18 - 40 % ] ( p<0.0001 ) . LIMITATIONS Some data were retrospective and subject to recall bias , and treatment was clinical ( non-r and omized ) . CONCLUSIONS The DMI course was strongly associated with first-episode depression or anxiety , excess depressive morbidity , and inferior treatment response , especially for depression
Comparison of manic symptoms across age groups suggested that irritability is a key feature of BD with an onset in childhood , activity is the most prominent in adolescent-onset BD and pressure of speech is more characteristic of adult-onset BD .
Conclusions Despite frequent discussion of similarities and differences in phenomenology of mania presenting in different age groups , systematic research is lacking and studies are still required to reliably establish whether the frequency and severity of manic symptoms varies .
Background In the last two decades , there has been a significant increase in the diagnosis of Bipolar Disorder ( BD ) in children .
The notion of prepubertal onsets of BD is not without controversy , with research ers debating whether paediatric cases have a distinct symptom profile or follow a different illness trajectory from other forms of BD .
The latter issue is difficult to address without long-term prospect i ve follow-up studies .
However , in the interim , it is useful to consider the phenomenology observed in groups of cases with different ages of onset and particularly to compare manic symptoms in children diagnosed with BD compared to cases presenting with BD in adolescence and adulthood .
This review systematic ally explores the phenomenology of manic or hypomanic episodes in groups defined by age at onset of BD ( children , adolescents and adults ; or combined age groups e.g. children and adolescents versus adults ) .