With Bipolr Disorder Annette M. Mtthews, MD; Vness B. Wilson, BA; Suznne H. Mitchell, PhD; nd Peter Huser, MD This study of smoking ehviors nd smoking chrcteristics in veterns with ipolr disorder contriutes useful dt to continue reserch into smoking nd its ssocited risk fctors, such s homelessness, lower eduction, nd crdiovsculr disese. In 2006, the prevlence of ipolr disorder mong veterns who use VHA fcilities nd clinics ws estimted t 4.4% of the tretmentseeking popultion. 1 This percentge compres with the estimted 1% to 5% of ipolr disorder prevlence in the generl popultion. 2 Militry service hs een found to increse cigrette smoking over lifespn, nd there re estimtes tht more thn 50% of veterns returning from Irq nd Afghnistn will return s. 3-5 Furthermore, veterns with ipolr disorder who seek tretment from the my hve greter rtes of dditionl smoking-ssocited risk fctors (eg, homelessness nd lower eduction). People with ipolr disorder, prticulrly those with ipolr depression, hve higher rtes of crdiovsculr disese, nd smoking is modifile risk fctor. 6,7 The Systemtic Tretment Enhncement Progrm for Bipolr Disorder (STEP-BD) ws multicenter study funded y the Ntionl Institute of Mentl Helth nd designed to evlute the longitudinl outcome of ptients with ipolr disorder. The overll study comined lrge prospective nturlistic study nd series of rndomized controlled trils. 8 Wxmonsky nd collegues performed comprisons etween current nd non on wide rry of vriles ville in the first 2,000 prticipnts in STEP-BD nd found severl vriles were ssocited in univrite mnner with current smoking, ut they did not go on to develop logistic regression models. 9 The gol of this study ws to develop logistic regression models to predict current smoking nd to differentite current from former in smple of veterns with ipolr disorder. For the vriles found significnt t the P.05 level y Wxmonsky nd collegues, the study uthors performed the sme univrite comprisons etween current nd current non (never nd former Dr. Mtthews is stff psychitrist in the Behviorl Helth nd Neurosciences Division of the Portlnd MC in Portlnd, Oregon. Dr. Mthews is lso n ssocite professor in the Deprtment of Psychitry nd Deprtment of Medicl Informtics nd Clinicl Epidemiology, Ms. Wilson is senior reserch ssistnt in the Deprtment of Behviorl Neuroscience, nd Dr. Mitchell is n ssocite professor in the Deprtment of Behviorl Neuroscience nd Deprtment of Psychitry, ll t Oregon Helth nd Science University in Portlnd. Dr. Huser is the VISN 22 Mentl Helth Services Led t the Long Bech Helthcre System in Long Bech, Cliforni. ) on the 121 U.S. veterns enrolled in the STEP-BD clinicl tril t the Portlnd MC (PMC). 9 This study then extended the work of tht pper (referred to s STEP 2,000) y developing logistic regression models using these cndidte vriles in smller smple of veterns with ipolr disorder. Finlly, these nlyses were repeted with the suset of former, to determine which vriles were predictive of continued smoking in this smple. The study uthors predicted tht only suset of risk fctors found in STEP 2,000 would e ssocited with incresed rtes of smoking in the susequent study, ecuse STEP 2,000 hd lrge smple size, which incresed the ility to detect significnt univrite comprisons. The uthors lso predicted tht some susets of these risk fctors would e significnt predictors of current smoking in their logistic regression model. In prticulr, it ws expected tht vriles such s current cffeine use, current sustnce use or dependence, lower income, lower eduction, nd history of suicide ttempt would e ssocited with current smoking, s these vriles re commonly ssocited with smoking. 10,11 Also predicted ws greter JUNE 2013 FEDERAL PRACTITIONER 23
Tle 1. Demogrphic dt: Current vs current non in ech smple All (N = 121) current STEP (N = 1,904 ) All STEP 2,000 current Totls (%) 121 51/121 (42.1) 1,904 594/1, 904 (31.2) P STEP P Bipolr sutype Bipolr I disorder (%) c 85 (70.2) 37 (43.5) 1,337 (70.3) 444 (33.2) Bipolr II disorder (%) 34 (28.1) 13 (38.2) 443 (23.3) 117 (26.4) =.597 =.2652 Bipolr NOS (%) 2 (1.7) 1 (50) 123 (6.4) 33 (26.6) =.856 =.4721 Employment Prt-time or unemployed 102 (84.3) 44 (43.1) 1,166 (66.3) 378 (32.4) =.611 =.0343 Full-time 19 (15.7) 7 (36.8) 593 (33.7) 163 (27.5) Gender Femle (%) 21 (17.4) 10 (47.6) 1,045 (58.1) 297 (28.4) =.577 =.0063 Mle (%) 100 (82.6) 41 (41.1) 753 (41.9) 259 (34.4) Rce d Nonwhite (%) 7 (5.8) 3 (42.9) 131 (7.3) 35 (26.7) =.984 =.2761 White (%) 113 (94.2) 48 (42.5) 1,668 (92.7) 522 (31.3) Dt were not ville for ll 1,904 sujects on ll vriles. See Wxmonsky (2005) for exct numers. 9 Wld chi-squre P vlue to test for ssocition etween specified vrile nd smoking in ech smple. c Reference ctegory. d Rce dt were not ville for 1 suject in the smple (N = 120). NOS = not otherwise specified; STEP = Systemtic Tretment Enhncement Progrm for Bipolr Disorder. smoking prevlence in this smple thn tht in the STEP 2,000 smple, due to the incresed prevlence of smoking mong veterns. Mterils nd Methods Study prticipnts were enrolled in STEP-BD t the PMC. STEP-BD required the prticipnts e ged > 15 yers nd meet the Dignostic nd Sttisticl Mnul of Mentl Disorders IV (DSM-IV) criteri for ipolr illness (ipolr I, ipolr II, cyclothymi, ipolr not otherwise specific [NOS], or schizoffective mnic or ipolr sutypes). A ttery of clinicl ssessment tools were dministered t study entry in order to determine clinicl sttus, severity of illness, numer of ffective episodes, nd presence of psychosis. The Clinicl Monitoring Form (CMF) ws the primry ongoing source of clinicl sttus informtion. 12 All instruments were dministered y trined rters. 8 Exclusion criteri were limited to the unwillingness or inility to comply with study ssessments or inility to give informed consent. At the PMC, 140 individuls met lifetime criteri of ipolr I, ipolr II, nd ipolr NOS (including cyclothymi) nd completed seline dignostic ssessments indicting smoking sttus. As in the STEP 2,000 study, schizoffective ptients (N = 8; 2 of which were lso nonveterns) were excluded from the smple s well s nonveterns (N = 13) for totl of 19 sujects excluded, leving 121 ptients in the smple of interest. The Institutionl Review Bord of the PMC gve its pprovl to conduct the STEP-BD study nd to nlyze the dt presented in this rticle. The uthors exmined the dt on the 121 eligile ptients enrolled in the STEP-BD clinicl tril t the PMC nd mde comprisons to the first 2,000 prticipnts in STEP- BD. Ptients were clssified s current, former, or never-, using dt collected from the initil clinicl ssessment 24 FEDERAL PRACTITIONER JUNE 2013
Tle 2. Vriles found predictive of current smoking in STEP 2,000 Vrile STEP 2,000 current P nd the initil CMF. Consistent with the previous smoking study on this dt set, ptients were clssified s current t the strt of the study if they smoked ny numer of cigrettes (recorded s pcks per dy) on entry into the STEP progrm for the 2 months prior to study entry. If prticipnts hd met the definition of current t some time in their life ut were not smoking t study entry, they were clssified s former ; otherwise, they were considered never-. The STEP 2,000 smple exmined current vs current non (former nd never) in univrite comprisons nd found the following 16 vriles significnt t the P.05 level: gender, eduction, employment, history of suicide ttempt, ge t study entry, ge t psychitric illness onset, Affective Disorder Evlution (ADE) depression score sum, ADE elevted mood sum, Montgomery-Aserg Depression Rting Scle (MADRS) totl score, Glol Assessment of Function (GAF) score, current cffeine use, current lcohol use, current illicit drug use, current nxiety disorder, pst nxiety disorder, nd typicl ntipsychotic currently prescried. Differences etween current nd current non for ech of these vriles were ssessed using univrite sttisticl tests. In ddition, the following 8 vriles were found significnt in the STEP 2,000 smple, ut meningful univrite tests in the mnner of STEP 2,000 could not e mde in the present study, ecuse cell sizes were too smll due in prt to the numer of ctegories used for the vriles: clinicl sttus, numer of lifetime depression phses, numer of lifetime mnic phses, rpid cycling within the pst yer, current psychotic symptoms, current ttention deficit-hyperctivity disorder (ADHD), pst ADHD, nd yerly income. Logistic regression techniques were used to develop models to predict current smoking s opposed to current nonsmoking. 13 These nlyses were repeted with the suset of former nd current, to determine which vriles were predictive of continued smoking in this smple. To nrrow the numer of vriles out of the hundreds ville in the STEP-BD dt set, only the vriles current P former P A DE depression score sum <.001 =.364 =.702 A DE elevted mood score =.001 =.136 =.543 sum Age t study entry <.001 =.104 =.111 A ge of psychitric illness <.001 =.285 =.486 onset Alcohol use, current =.012 =.149 =.259 Anxiety disorder, current <.001 =.686 =.719 Anxiety disorder, pst =.031 =.944 =.872 A typicl ntipsychotic =.038 =.975 =.978 prescried C ffeine use, current <.001 =.005 =.010 (cups per dy) Eduction <.001 =.006 =.013 Employment =.034 =.611 =.489 GAF <.001 =.271 =.387 Gender =.006 =.577 =.946 History of suicide ttempts <.001 =.030 =.022 I llicit drug use, current <.001 =.084 =.065 MADRS totl score =.001 =.169 =.369 ADE = Affective Disorder Evlution; GAF = Glol Assessment of Functioning scle; MADRS = Montgomery-Aserg Depression Rting Scle; STEP = Systemtic Tretment Enhncement Progrm for Bipolr Disorder. found significnt in the STEP 2,000 smple were considered s cndidte vriles. Although not considered for inclusion in the regression modeling, the uthors lso looked t current nd pst lcohol nd drug dependence, rpid cycling, nd history of suicide ttempt nd exmined whether these vriles were independently relted to current smoking. Results There were totl of 121 persons JUNE 2013 FEDERAL PRACTITIONER 25
Tle 3. Univrite logistic regression results for the cndidte vriles to predict current smoking Vrile Current Current non Odds rtio 95% CI (rnge) Wld χ 2 df P A DE elevted mood 0.907 (1.317) 0.600 (0.894) 1.293 0.922-1.813 2.224 1 =.136 score sum (%) Age t STEP entry (%) 47.060 (11.5) 50.700 (12.4) 0.975 0.945-1.005 2.651 1 =.104 C ups of cffeine 4.410 (4.30) 2.500 (2.37) 1.199 1.057-1.361 7.897 1 =.005 per dy (%) Current lcohol use Current lcohol use (%) No current lcohol use c 34 55 16 14 1.849 0.802-4.261 2.080 1 =.149 Current illicit drug use C urrent illicit drug 11 7 2.475 0.886-6.913 2.990 1 =.084 use (%) N o current illicit 40 63 drug use c Eduction 10.237 2 =.006 High school or less 18 10 6.429 2.056-20.104 10.231 1 =.001 S ome college/ 26 35 2.653 0.996-7.067 3.810 1 =.051 technicl/ssocite degree C ollege grdute/ 7 25 professionl c H istory of suicide ttempts H istory of suicide 31 28 2.270 1.083-4.755 4.719 1 =.030 ttempts N o history of suicide 20 41 ttempts c MADRS totl score (%) 15.4 (10.0) 13.100 (8.5) 1.028 0.988-1.070 1.889 1 =.169 Continuous vrile presented s men +/- stndrd devition, ctegoricl s N (%). Dt were not ville for 5 sujects (N = 116). c Reference ctegory. ADE = Affective Disorder Evlution; CI = confidence intervl; df = degrees of freedom; MADRS = Montgomery-Aserg Depression Rting Scle; STEP = Systemtic Tretment Enhncement Progrm for Bipolr Disorder. with ipolr disorder enrolled in STEP-BD t PMC (19 ptients with schizoffective disorder or who were nonveterns were excluded), nd dt on tocco use ws ville for ll prticipnts. The men ge t study entry ws 49.2 yers (stndrd devition = 12.1). Fiftyone prticipnts (42.1%) reported tht they were current ; 42 prticipnts (34%) reported tht they were former ; nd 28 prticipnts (23.1%) reported tht they hd never smoked (never). The lifetime prevlence of smoking (current nd former ) ws 76.9% (N = 93) (Tle 1 shows comprisons of the current nd STEP 2,000 current ). Of the 51 current in the study, 26 FEDERAL PRACTITIONER JUNE 2013
Tle 4. Finl logistic regression model for prediction of current smoking Vrile B SE Wld df P Odds rtio 95% CI (rnge) Cups of cffeine per dy 0.203 0.07 8.321 1 =.004 1.225 1.067-1.406 Eduction 10.303 2 =.006 High school or less 1.936 0.603 10.302 1 =.001 6.931 2.125-22.608 S ome college/technicl/ssocite degree College grdute/professionl 1.038 0.52 3.987 1 =.046 2.823 1.019-7.82 Constnt -1.966 0.505 15.129 1 =.001 0.14 Model χ 2 (3) = 21.192, P <.001; R 2 = 0.164, Cox & Snell R2 = 0.221. Ngelkerke Reference ctegory. CI = confidence intervl; df = degrees of freedom; SE = stndrd error. 37.3% (n = 19) hd current lcohol use or dependence, 19.6% (n = 10) hd current drug use or dependence, nd 60.8% (n = 31) hd history of suicide ttempt. Only 4% (n = 2) of the 50 current with dt exhiited rpid cycling. The smple hd significntly higher proportion of current, higher proportion of men, nd lower proportion of sujects in fulltime employment thn did those of the STEP-BD smple. Current. Of the 121 veterns, 100 (82.6%) were men (Tle 1). Men were no more likely to e thn were women (P =.577). Univrite nlyses were run on the 16 vriles identified s predictive of smoking in the STEP 2,000 dt if cell sizes permitted (Tle 2). Using P.25 s cutoff point for STEP 2,000 vriles tht could e considered for the logistic regression model, cndidte vriles for the model were determined to predict current smoking. Being current smoker ws significntly ssocited with lower eduction (P =.006), drinking more cffeine (P =.005), nd hving history of suicide ttempt (P =.030). In ddition, greter ge t study entry, incresed ADE elevted mood scores, incresed MADRS totl scores, current lcohol use, nd current illicit drug use were predictive of current smoking t the P.25 significnce level nd were considered s cndidte vriles (Tle 3 shows the sttistics of these 8 cndidte vriles). The study gol ws to develop the est predictive model possile, while keeping the model sttisticlly significnt. Model development proceeded y first forcing ll these 8 vriles into forced model. From the forced model, 2 vriles were le to e identified tht were significnt predictors of current smoking in the predictive model: cups of cffeine per dy nd level of eduction. The sme model ws otined using forwrd selection procedure (Tle 4 shows the finl logistic regression model, including these vriles [P <.001]). Additionl nlyses indicted tht current were more likely thn current non to hve history of lcohol dependence (: 62.7%; non: 40.0%, χ 2 (1) = 6.106, P =.013), e currently lcohol dependent (: 17.6%; non: 4.3%, χ 2 (1) = 5.896, P =.015), nd hve history of drug dependence (: 41.2%; non: 18.6%, χ 2 (1) = 7.462, P =.006). Current drug dependence ws not relted to current smoking; however, few sujects were currently drug dependent (: 5.9%; non: 4.3%, P >.05). Rtes of rpid cycling were low nd did not differ etween current nd non (: 4.0%; non: 10.6%, χ 2 (1) = 1.734, P >.05). However, history of suicide ttempts ws significnt predictor of current smoking (: 60.8%; non: 40.6%, χ 2 (1) = 4.790, P =.029). Finlly, use of upropion, nonupropion ntidepressnt, or ny ntidepressnt ws not ssocited with current smoking (P >.05). Former. Within the suset of 93 ever, 42 were former nd 51 were current. Demogrphic dt for the 42 former re presented in Tle 5. Univrite nlyses compring former nd current on the vriles found significnt in the STEP 2,000 smple re presented in Tle 2. As efore, using P.25 s cutoff point for vriles to e considered in logistic regression model, 5 cndidte vriles were identi- JUNE 2013 FEDERAL PRACTITIONER 27
Tle 5. Demogrphic dt: Current vs former fied tht were predictive of continued smoking: lower eduction (P =.006), history of suicide ttempts (P =.022), incresed ge (P =.111), current cffeine use (P =.010), nd current illicit drug use (P =.065). Tle 6 illustrtes the detils of the univrite nlysis for ech of these vriles. Using the sme vrile selection methods descried erlier, model ws otined tht included the numer of cups of cffeine per dy nd level of eduction. Specificlly, lower eduction nd greter cffeine intke were ssocited with continued smoking (Model χ 2 (3) = 19.749, P =.001; R 2 Cox & Snell = 0.191, R2 Ngelkerke = 0.256). Additionl nlyses indicted tht current nd pst lcohol dependence (N = 93 ever ) Current Former Totls 51 42 Bipolr sutype Bipolr I disorder 37 32 Bipolr II disorder 13 9 Bipolr NOS 1 1 Employment Prt-time or unemployed 44 34 =.489 Full-time 7 8 Gender Femle 10 8 =.946 Mle 41 34 Rce Nonwhite (%) 3 4 White (%) 48 38 Wld chi-squre P vlue to test for ssocition etween specified vrile nd smoking in ech smple. Cell size too smll to clculte. NOS = not otherwise specified. P were not relted to continued smoking (P >.05), nd wheres current rtes of drug dependence were low in oth groups nd not relted to continued smoking, pst drug dependence ws relted to continued smoking (current : 41.2%; former : 21.4%, χ 2 (1) = 4.110, P <.043). Similr to the erlier nlysis compring current with current non, rpid cycling ws not relted to continued smoking (current : 4.0%; former : 10.3%, P >.05). However, history of suicide ttempt ws significnt predictor of continued smoking (current : 60.8%; former : 36.6%, χ 2 (1) = 5.324, P =.021). Finlly, former were more likely thn continuing to e on n ntidepressnt (either upropion or nonupropion) (current : 41.2%; former : 61.9%, χ 2 (1) = 3.959, P <.047). Discussion A significntly higher proportion of the STEP-BD sujects enrolled through the PMC reported they were current compred with those enrolled in the STEP 2,000 smple, indicting tht veterns with ipolr disorder smoke t higher rte thn do nonveterns with ipolr disorder. This result ws consistent with previous studies. 2 This study smple lso included fewer women nd those with less employment, likely reflective of the smple t lrge. Mny fctors tht were found to e significnt univrite predictors of current smoking in the STEP 2,000 smple were not found to e significnt in this nlysis. This is likely due in prt to lower power ecuse of the smller smple size in the dt set compred with the STEP 2,000 smple. Level of eduction nd cups of cffeine per dy were significntly ssocited with current nd continued smoking in the study logistic regression models. Incresed cffeine use is significntly ssocited with incresed odds of current smoking, which suggests tht veterns should e encourged to reduce or eliminte their use of cffeine s prt of successful smoking cesstion intervention. This is consistent with the literture showing tht quitting lcohol use t the sme time s quitting smoking increses smoking stinence nd suggests tht there my e role for further reserch into how reduction in cffeine use my id in smoking cesstion. 5,14 This popultion is more likely to hve multiple poor heth ehviors tht need in- 28 FEDERAL PRACTITIONER JUNE 2013
Tle 6. Univrite logistic regression results for the cndidte vriles to predict current smoking vs former smoking Vrile Wld χ 2 df P Current Former Odds rtio 95% CI (rnge) Age t STEP entry (%) 47.06 (11.5) 51.24 (13.35) 0.973 0.940-1.006 2.540 1 =.111 Cups of cffeine per dy (%) 4.41 (4.30) 2.30 (2.12) 1.241 1.054-1.461 6.714 1 =.010 Current illicit drug use Current illicit drug use 11 3 3.575 0.926-13.799 3.418 1 =.065 No current illicit drug use 40 39 Eduction 8.047 2 =.018 High school or less 18 6 6.429 1.773-23.303 8.020 1 =.005 S ome college/technicl/ 26 21 2.653 0.914-7.701 3.810 1 =.073 ssocite degree C ollege grdute/ 7 15 professionl History of suicide ttempts History of suicide 31 15 2.687 1.150-6.276 5.212 1 =.022 ttempts N o history of suicide ttempts 20 26 Continuous vrile presented s men +/- SD, ctegoricl s N. Reference ctegory. CI = confidence intervl; df = degrees of freedom; SD = stndrd devition; STEP = Systemtic Tretment Enhncement Progrm for Bipolr Disorder. tervention, nd tilored progrms to ddress cffeine use in this popultion would e eneficil. Success t n ctivity such s stopping or reducing cffeine use cn uild self-efficcy tht my e useful when trying to stop more ddictive sustnce like tocco. 15-17 This study supports the lredy known ssocition etween low eductionl sttus nd smoking. The study dt lso indicte tht higher eduction is ssocited with smoking cesstion mong ever (Tle 6). This suggests tht interventions for smoking cesstion should e intensified for those with lower eduction, nd eductionl level should e tken into ccount when counseling out smoking. 18,19 In ddition to the vriles found to e significnt in the STEP 2,000 pper, this study exmined severl other vriles of potentil interest. Of the current, 32.0% used lcohol compred with 34.4% in the STEP 2,000 smple, nd 21.6% used other illicit sustnces, compred with 54.0% in STEP 2,000. 9 The much lower rtes of illicit sustnce use in this study smple likely reflect tht this is n older group, nd mny of them re likely in recovery. Although STEP 2,000 did not exmine the rtes of current dependence, these dt lso showed significntly higher rtes pst drug dependence in current nd in continued. This study lso concluded tht current nd pst lcohol were ssocited with current smoking (P <.05), suggesting tht these my e risk fctors for smoking in this popultion. Rtes of history of suicide ttempts were significntly higher in the study smple of current thn in current non nd mong the suset of ever tht continue to smoke thn in those who hd quit smoking. Smoking hs previously een shown to e ssocited with suicide, nd this reconfirms tht finding. 20 This lso suggests tht it my e prticulrly importnt to council returning veterns on smoking cesstion s mens of decresing their risk of suicide. STrengths nd Limittions The strengths of this study included using dt collected y lrge N- JUNE 2013 FEDERAL PRACTITIONER 29
tionl Institute of Mentl Helthfunded nturlistic study of ipolr disorder, which used trined rters with rigorous techniques for dt collection, entry, clening, nd storge. 8 Limittions of the study included smll smple size nd tht the prticulr smple is mostly Vietnm-er veterns. Also, the models generted my not e generlizle to the veterns of more recent ers. There is need for further study of more recent er veterns, prticulrly s smoking ecomes less cceptle in the militry nd in the culture t lrge. Conclusion This study expnded on the STEP 2,000 study y using cndidte vriles derived from tht study to chrcterize risk fctors for current smoking in veterns with ipolr disorder. The uthors elieve tht this study is the only one tht looks t U.S. veterns tht were enrolled in the STEP-BD study nd tht uses the results of the previous study (STEP 2,000). Using STEP 2,000 in this wy guided dt nlyses nd llowed the uthors to suggest similrities nd differences etween the vetern popultion nd generl popultion, which might e useful in future tretment nd future studies. The results suggested tht reducing cffeine drinking my improve smoking cesstion outcomes nd replictes the ssocition etween level of eduction nd smoking tht hs een seen in previous literture. Future reserch should look t the effect of ntidepressnts nd other psychotropic medictions on smoking nd smoking cesstion nd whether specific helth interventions tht trget reducing cffeine led to etter outcomes with eventul smoking cesstion. Acknowledgments This work ws done s prt of Veterns Affirs Creer Development Awrd, NIH grnts DA0145543 nd DA024195, nd Veterns Affirs Merit Review Awrd. Author disclosures Peter Huser received reserch support from Jnssen Phrmceuticls, Inc., the U.S. Veterns Affirs Administrtion, nd the Ntionl Institute of Mentl Helth. He is on the speker s ureu for AstrZenec Phrmceuticls. The other uthors report no ctul or potentil conflicts of interest with regrd to this rticle. Disclimer The opinions expressed herein re those of the uthors nd do not necessrily reflect those of Federl Prctitioner, Qudrnt HelthCom Inc., division of Frontline Medicl Communictions Inc., the U.S. Government, or ny of its gencies. This rticle my discuss unleled or investigtionl use of certin drugs. Plese review complete prescriing informtion for specific drugs or drug comintions including indictions, contrindictions, wrnings, nd dverse effects efore dministering phrmcologic therpy to ptients. References 1. Blow FC, McCrthy JF, Vlenstein M, Visnic S, Gillon L. Cre for Veterns With Psychosis in the Veterns Helth Administrtion, FY06: 8th Annul Ntionl Psychosis Registry. Ann Aror, MI: Serious Mentl Illness Tretment Reserch nd Evlution Center (SMITREC); 2007. 2. Akiskl HS, Pinto O. The evolving ipolr spectrum: Prototypes I, II, III, nd IV. 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