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The effect of substance abuse on the course of bipolar disorder
Abstrncts
mOL PSYCHIATRY
617
1995:39:500-666
401. ALCOHOLISM AND AGE INTERACT IN THEIR EFFECTS ON BRAIN FUNCTION J.M. Ford', D.H. Mathalon', MJ. Rosenbloon 2 , K.O. Lim 1•2 , & A. Pfefferbaum J•2 IStOlnford University School of Medicine. Stanford, CA. 94305~ 2VA·Palo Alto Heallh C3fC System. Palo Allo, CA 94304 Since its discovery by Sutton <;t lll. (1965) 30 years ago. the P300 component of the event related brain potential (ERP) hns been shown to be altered in a number of psychiatric illnesses. In particulnr. its tutency is delayed with normal rlging (Pfeffr.rbnum et aI., 1984) and in patients with alcoholism (Pfcfferbaum et al.. 1991). Here. we cKuminc the relationship of 1'300 1;1Iency to ugc in alcoholic men and controls. Thirty-seven :lIcoholic men and 32 age.malched nannal control men were tested on an auditory oddball paradigm in which subjects pressed a button to infrequent tones and ignored frequent tones. 1'300 latenc)' to the infrequent tones WllS measured. nnd infomllltion regarding years of alcoholic drinking nnd the amount of alcohol consumed was also collected. Using II multiple lincar regression nnalysis, we found P300 l:lIency wa~ dclllycd with llge (p<.02) and alcoholism (p<.04), and there was an llge by alcoholism interaclion (p<.05). This paUern suggested that age effects on P300 latency arc gre:lIcr in alcoholics than comrols. Within alcoholics. neither duration of alcoholic drinking nor amount drunk accounted for the steeper age·related increase in P300 latency seen in llicoholics. In controls. amount drunk also did not mediate effects of age on P300 latency. The data suggest that alcoholism nnd age internct in their effects on brnin function. These effects do not nppcar 10 be medillted by simple. cumulative alcohol exposure, but might be innuenced by other a~pects of the alcoholism syndrome and age·related sU5ccptibility of the brain to alcohol. Supported by NIAAA (AAOS965) & Departmcnl of Veterans Affairs.
402. THE PREDICTION OF ALCOHOLISM A DECADE LATER M.A. Schuckit San Diego Veterans Affairs Medical Center, Univcrsity of Clllifomia San Diego Medical School, San Diego. CA Cross-scctionlll comparisons of sons of alcoholics and controls have revealed evidence of a lower intensity of response to alcohol in the children of alcohol dependant men. Evidence or n lower response wao; documcntcd in alcohol-induccd subjecfive feelings. changes in mOlor performance. allerations in hormones, and ciectrophysioiogiclli measures, and results were observed even afler controlling for recent drinking and drug use histories a:; well as hlood alcohol concenlrations during the evaluation. Almost a decade IIftcr initial testing. all 453 subjCCl~ were locatcd, and follow-up data obtained on 450 men. A low level of response to nlcoholat approximotely age 20 was found 10 be a significant predictor of later alcoholism, operating a... on apparent mediotor of risk. The relationship between the level of response nnd alcoholic outcome remained robust aner considering the impact of Ibe quantity and frequcncy of drinking earlier in !ife. Neither family history or olcoholism uar level of response to un alcohol cbllllenge pl'Cflicled depressh'e or anxiety disorders, nor did prior levels of aoxicty or deprcssinr. predict alcoholic outcome. While members of both fllmily history groups hlld exposure 10 other drugs of abuse during the fallaw-up period, they did not differ significnntly on the development of drug dependence. nllhough
there wus a lrend for lln increased risk for cocaine-related disorders in lhe sons of alcoholics.
404. THE EFFECT OF SUBSTANCE ABUSE ON THE COURSE OF BIPOLAR DISORDER D.L. Dunner & J. Feinman Deplll1mcnl of Psychiatry and Behavioral Schmces. University of Washington, ScoUle, \VA. 98105-6099 We reviewed the clinical records of 188 patients who had a diagnosis of bipolar disorder. Plltients were separated into three groups: those who had bipolar disorder uncomplicated by substance or alcohol abuse (103 subjects "primary uncomplicnced"); patients who had bipolar disorder subsequently complicated by llicohol or subs lance abuse (35 subjects "complicated"); and SO subjects who hnd n primnry di3snosis of substance abuse and who subsequently developed bipolar disorder ("second:uy"). Subjects were also scparnled as bipolar I, bipolar II, nnd cyclothymic and charnclcrized by eycle frequency. The major findings suggest that complicaled bipolar patients had the earliest age of onset suggesting thut early onset bipolar disorder puts individuals at risk (or subsequent substance nDuse. Cycle frequencies seem to be highest in the secondary and complicated groups. Some of lhe behavioral ratings suggest that a history ofsubstance abuse increased severity of depression as measured during the clinical inlcrvicw. Family history data suggest that the complicated and secondary groups had higher morbid risks for alcohol and substance abuse among first degree relatives than did the primary uncomplicated group.
405. GROWTH HORMONE RESPONSE TO SUMATRIPTAN (5~HTID AGONIST) CHALLENGE IN SAD: EFFECTS OF LIGHT
THERAPY
L.N. Yatham, R.W. Lam, & A.P. Zis The University of British Columbia. V3ncouvcr. British Columbia. Canada There has been on increasing intcrest in the rote of serotonin in the pathophyliiology of seasonal lIffcclivc disorder and lhe mechnnism of :lction of light therapy. To furlher explore the role of the seTOtonergic system in sea.~onal affective disorder. we compnred growth honnone (GH) responses to a challenge with II novel S-H I0 receptor ngonist sumatriptan. between patients with sea.~onal llffective (.lisordcr and healthy controls Dnd within patiems with 5easonol affective disorder before and after light Ihernpy. Study subjects Included cleven drug free patients who met OSM-lV c:riterill for recurrent major depressive episodes with n sensonal pattern, and twelve healthy controls. Subjects pi.::scntcd for lCliilng nf:er ~'1 Qvr.mighl fll'it. After nh~aining n blood sample for haseline GH levels. sumatriptan 6 mg I" .ven sulx:utaneoURly. and further blood samples were collected at I.... l ilour intcl"Vals for 2 hours. Patients with seasonnl depression were trented with lisht Ihempy. ond sumntriptnn challenge W:lS repeated within 3 - 6 weeks or commencement of light therapy. OH responses in patientll with seasonal nffective di50rdcr were significantly blunted compared to healthy con- . trois. The OH responscs in pallents with sellsonal nrrective disorder
mOL PSYCHIATRY
617
1995:39:500-666
401. ALCOHOLISM AND AGE INTERACT IN THEIR EFFECTS ON BRAIN FUNCTION J.M. Ford', D.H. Mathalon', MJ. Rosenbloon 2 , K.O. Lim 1•2 , & A. Pfefferbaum J•2 IStOlnford University School of Medicine. Stanford, CA. 94305~ 2VA·Palo Alto Heallh C3fC System. Palo Allo, CA 94304 Since its discovery by Sutton <;t lll. (1965) 30 years ago. the P300 component of the event related brain potential (ERP) hns been shown to be altered in a number of psychiatric illnesses. In particulnr. its tutency is delayed with normal rlging (Pfeffr.rbnum et aI., 1984) and in patients with alcoholism (Pfcfferbaum et al.. 1991). Here. we cKuminc the relationship of 1'300 1;1Iency to ugc in alcoholic men and controls. Thirty-seven :lIcoholic men and 32 age.malched nannal control men were tested on an auditory oddball paradigm in which subjects pressed a button to infrequent tones and ignored frequent tones. 1'300 latenc)' to the infrequent tones WllS measured. nnd infomllltion regarding years of alcoholic drinking nnd the amount of alcohol consumed was also collected. Using II multiple lincar regression nnalysis, we found P300 l:lIency wa~ dclllycd with llge (p<.02) and alcoholism (p<.04), and there was an llge by alcoholism interaclion (p<.05). This paUern suggested that age effects on P300 latency arc gre:lIcr in alcoholics than comrols. Within alcoholics. neither duration of alcoholic drinking nor amount drunk accounted for the steeper age·related increase in P300 latency seen in llicoholics. In controls. amount drunk also did not mediate effects of age on P300 latency. The data suggest that alcoholism nnd age internct in their effects on brnin function. These effects do not nppcar 10 be medillted by simple. cumulative alcohol exposure, but might be innuenced by other a~pects of the alcoholism syndrome and age·related sU5ccptibility of the brain to alcohol. Supported by NIAAA (AAOS965) & Departmcnl of Veterans Affairs.
402. THE PREDICTION OF ALCOHOLISM A DECADE LATER M.A. Schuckit San Diego Veterans Affairs Medical Center, Univcrsity of Clllifomia San Diego Medical School, San Diego. CA Cross-scctionlll comparisons of sons of alcoholics and controls have revealed evidence of a lower intensity of response to alcohol in the children of alcohol dependant men. Evidence or n lower response wao; documcntcd in alcohol-induccd subjecfive feelings. changes in mOlor performance. allerations in hormones, and ciectrophysioiogiclli measures, and results were observed even afler controlling for recent drinking and drug use histories a:; well as hlood alcohol concenlrations during the evaluation. Almost a decade IIftcr initial testing. all 453 subjCCl~ were locatcd, and follow-up data obtained on 450 men. A low level of response to nlcoholat approximotely age 20 was found 10 be a significant predictor of later alcoholism, operating a... on apparent mediotor of risk. The relationship between the level of response nnd alcoholic outcome remained robust aner considering the impact of Ibe quantity and frequcncy of drinking earlier in !ife. Neither family history or olcoholism uar level of response to un alcohol cbllllenge pl'Cflicled depressh'e or anxiety disorders, nor did prior levels of aoxicty or deprcssinr. predict alcoholic outcome. While members of both fllmily history groups hlld exposure 10 other drugs of abuse during the fallaw-up period, they did not differ significnntly on the development of drug dependence. nllhough
there wus a lrend for lln increased risk for cocaine-related disorders in lhe sons of alcoholics.
404. THE EFFECT OF SUBSTANCE ABUSE ON THE COURSE OF BIPOLAR DISORDER D.L. Dunner & J. Feinman Deplll1mcnl of Psychiatry and Behavioral Schmces. University of Washington, ScoUle, \VA. 98105-6099 We reviewed the clinical records of 188 patients who had a diagnosis of bipolar disorder. Plltients were separated into three groups: those who had bipolar disorder uncomplicated by substance or alcohol abuse (103 subjects "primary uncomplicnced"); patients who had bipolar disorder subsequently complicated by llicohol or subs lance abuse (35 subjects "complicated"); and SO subjects who hnd n primnry di3snosis of substance abuse and who subsequently developed bipolar disorder ("second:uy"). Subjects were also scparnled as bipolar I, bipolar II, nnd cyclothymic and charnclcrized by eycle frequency. The major findings suggest that complicaled bipolar patients had the earliest age of onset suggesting thut early onset bipolar disorder puts individuals at risk (or subsequent substance nDuse. Cycle frequencies seem to be highest in the secondary and complicated groups. Some of lhe behavioral ratings suggest that a history ofsubstance abuse increased severity of depression as measured during the clinical inlcrvicw. Family history data suggest that the complicated and secondary groups had higher morbid risks for alcohol and substance abuse among first degree relatives than did the primary uncomplicated group.
405. GROWTH HORMONE RESPONSE TO SUMATRIPTAN (5~HTID AGONIST) CHALLENGE IN SAD: EFFECTS OF LIGHT
THERAPY
L.N. Yatham, R.W. Lam, & A.P. Zis The University of British Columbia. V3ncouvcr. British Columbia. Canada There has been on increasing intcrest in the rote of serotonin in the pathophyliiology of seasonal lIffcclivc disorder and lhe mechnnism of :lction of light therapy. To furlher explore the role of the seTOtonergic system in sea.~onal affective disorder. we compnred growth honnone (GH) responses to a challenge with II novel S-H I0 receptor ngonist sumatriptan. between patients with sea.~onal llffective (.lisordcr and healthy controls Dnd within patiems with 5easonol affective disorder before and after light Ihernpy. Study subjects Included cleven drug free patients who met OSM-lV c:riterill for recurrent major depressive episodes with n sensonal pattern, and twelve healthy controls. Subjects pi.::scntcd for lCliilng nf:er ~'1 Qvr.mighl fll'it. After nh~aining n blood sample for haseline GH levels. sumatriptan 6 mg I" .ven sulx:utaneoURly. and further blood samples were collected at I.... l ilour intcl"Vals for 2 hours. Patients with seasonnl depression were trented with lisht Ihempy. ond sumntriptnn challenge W:lS repeated within 3 - 6 weeks or commencement of light therapy. OH responses in patientll with seasonal nffective di50rdcr were significantly blunted compared to healthy con- . trois. The OH responscs in pallents with sellsonal nrrective disorder