Department of Psychology Works

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    The neurobiology of alcoholism in genetically selected rat models
    (The National Institute on Alcohol Abuse and Alcoholism, 1997) Stewart, Robert B.; Li, Ting-Kai; Psychology, School of Science
    Rats selectively bred for their tendency to drink large or small quantities of alcohol are a useful model for investigators examining the possible neurobiological processes underlying alcoholism. Studies with the alcohol-preferring (P) and alcohol-nonpreferring (NP) and the high-alcohol-drinking (HAD) and low-alcohol-drinking (LAD) pairs of rat lines developed at Indiana University have illustrated differences in several behavioral and neurobiological characteristics associated with alcohol consumption. Specifically, compared with alcohol-avoiding rats, rats with an affinity for alcohol have a greater sensitivity to the stimulatory effects of low to moderate doses and a reduced sensitivity to the negative effects of high doses. Rats that voluntarily drink large quantities of alcohol also acquire tolerance to alcohol’s aversive effects. In addition, these rats differ from their alcohol-avoiding counterparts in the levels of several chemical mediators (i.e., neurotransmitters) found in the brain, including serotonin, dopamine, gamma-aminobutyric acid (GABA), and the endogenous opioids.
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    Mechanisms of alcohol-induced damage to the developing nervous system
    (The National Institute on Alcohol Abuse and Alcoholism, 2001) Goodlett, Charles R.; Horn, Kristin H.; Psychology, School of Science
    Numerous mechanisms likely contribute to the damaging effects of prenatal alcohol exposure on the developing fetus and particularly the developing central nervous system (CNS). The coexistence of a multitude of mechanisms that may act simultaneously or consecutively and differ among various cell types poses particular challenges to researchers. To study alcohol’s effects on the fetus more easily, investigators have used animal models and tissue-culture experiments. Such approaches have identified numerous potential mechanisms through which alcohol acts on the fetus, many of which result in cell death by necrosis or apoptosis. Among these mechanisms are increased oxidative stress, damage to the mitochondria, interference with the activity of growth factors, effects on glia cells, impaired development and function of chemical messenger systems involved in neuronal communication, changes in the transport and uptake of the sugar glucose, effects on cell adhesion, and changes in the regulation of gene activity during development.
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    GABA(A) receptors containing (alpha)5 subunits in the CA1 and CA3 hippocampal fields regulate ethanol-motivated behaviors: an extended ethanol reward circuitry
    (Society for Neuroscience, 2001-03-15) June, Harry L.; Harvey, Scott C.; Foster, Katrina L.; McKay, Peter F.; Cummings, Rancia; Garcia, Marin; Mason, Dynesha; Grey, Collette; McCane, Shannan; Williams, La Shone; Johnson, Timothy B.; He, Xiaohui; Rock, Stephanie; Cook, James M.; Psychology, School of Science
    GABA receptors within the mesolimbic circuitry have been proposed to play a role in regulating alcohol-seeking behaviors in the alcohol-preferring (P) rat. However, the precise GABA(A) receptor subunit(s) mediating the reinforcing properties of EtOH remains unknown. We examined the capacity of intrahippocampal infusions of an alpha5 subunit-selective ( approximately 75-fold) benzodiazepine (BDZ) inverse agonist [i.e., RY 023 (RY) (tert-butyl 8-(trimethylsilyl) acetylene-5,6-dihydro-5-methyl-6-oxo-4H-imidazo [1,5a] [1,4] benzodiazepine-3-carboxylate)] to alter lever pressing maintained by concurrent presentation of EtOH (10% v/v) and a saccharin solution (0.05% w/v). Bilateral (1.5-20 microgram) and unilateral (0.01-40 microgram) RY dose-dependently reduced EtOH-maintained responding, with saccharin-maintained responding being reduced only with the highest doses (e.g., 20 and 40 microgram). The competitive BDZ antagonist ZK 93426 (ZK) (7 microgram) reversed the RY-induced suppression on EtOH-maintained responding, confirming that the effect was mediated via the BDZ site on the GABA(A) receptor complex. Intrahippocampal modulation of the EtOH-maintained responding was site-specific; no antagonism by RY after intra-accumbens [nucleus accumbens (NACC)] and intraventral tegmental [ventral tegmental area (VTA)] infusions was observed. Because the VTA and NACC contain very high densities of alpha1 and alpha2 subunits, respectively, we determined whether RY exhibited a "negative" or "neutral" pharmacological profile at recombinant alpha1beta3gamma2, alpha2beta3gamma2, and alpha5beta3gamma2 receptors expressed in Xenopus oocytes. RY produced "classic" inverse agonism at all alpha receptor subtypes; thus, a neutral efficacy was not sufficient to explain the failure of RY to alter EtOH responding in the NACC or VTA. The results provide the first demonstration that the alpha5-containing GABA(A) receptors in the hippocampus play an important role in regulating EtOH-seeking behaviors.
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    The GABA(A) receptor alpha1 subtype in the ventral pallidum regulates alcohol-seeking behaviors
    (Society for Neuroscience, 2002-05-01) Harvey, Scott C.; Foster, Katrina L.; McKay, Pete F.; Carroll, Michelle R.; Seyoum, Regat; Woods, James E., II; Grey, Collette; Jones, Cecily M.; McCane, Shannan; Cummings, Rancia; Mason, Dynesha; Ma, Chunrong; Cook, James M.; June, Harry L.; Psychology, School of Science
    We investigated the potential role of the alpha1-containing GABA(A) receptor in regulating the reinforcing properties of alcohol. To accomplish this, we developed 3-propoxy-beta-carboline hydrochloride (3-PBC), a mixed agonist-antagonist benzodiazepine site ligand with binding selectivity at the alpha1 receptor. We then tested the capacity of 3-PBC to block alcohol-maintained responding in the ventral pallidum (VP), a novel alcohol reward substrate, which primarily expresses the alpha1-receptor isoform. Our results demonstrated that bilateral microinfusion of 3-PBC (0.5-40 microg) in the anterior and medial VP produced marked reductions in alcohol-maintained responding in a genetically selected rodent model of alcohol drinking. The VP infusions showed both neuroanatomical and reinforcer specificity because no effects were seen in sites dorsal to the VP (e.g., nucleus accumbens, caudate putamen). The saccharin-maintained responding was reduced only with the highest dose (40 microg). Parenteral injections of 3-PBC (1-20 mg/kg) also showed a similar selectivity on alcohol-maintained responding. Complementary in vitro studies revealed that 3-PBC exhibited a low partial agonist efficacy profile at recombinant diazepam-sensitive receptors (e.g., alpha1beta3gamma2, alpha2beta3gamma, and alpha3beta3gamma2). The selective suppression of 3-PBC on alcohol-maintained responding after central and parenteral administrations, together with its low-efficacy agonist profile, suggest that the reduction in alcohol-maintained behaviors was not attributable to a general suppression on consummatory behaviors. These results demonstrate that the alpha1-containing GABA(A) receptors in both the anterior and medial VP are important in regulating the reinforcing properties of alcohol. These receptors represent novel targets in the design and development of pharmacotherapies for alcohol-dependent subjects.
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    Clinical and Psychological Correlates of Two Domains of Hopelessness in Schizophrenia
    (2008-12) Lysaker, Paul H.; Salyers, Michelle P.; Tsai, Jack; Spurrier, Linda Yorkman; Davis, Louanne W.
    Hopelessness is a widely observed barrier to recovery from schizophrenia spectrum disorders. Yet little is known about how clinical, social, and psychological factors independently affect hope. Additionally, the relationships that exist between these factors and different kinds of hope are unclear. To explore both issues, we correlated two aspects of hope, expectations of the future and agency, with stigma, clinical symptoms, anxiety, and coping preferences in 143 persons with a schizophrenia spectrum disorder. Multiple regressions revealed that hope for the future was predicted by lesser alienation, lesser preference for ignoring stressors, and lesser emotional discomfort and negative symptoms, accounting for 43% of the variance. A greater sense of agency was linked to lesser endorsement of mental illness stereotypes, fewer negative symptoms, lesser social phobia, and lesser preference for ignoring stressors, accounting for 44% of the variance. Implications for research and interventions are discussed.
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    The Role of Patient Activation in Psychiatric Visits
    (2009-11) Salyers, Michelle P.; Matthias, Marianne S.; Spann, Crystal; Lydick, Jennifer; Rollins, Angela L.; Frankel, Richard M.
    OBJECTIVE: This study identified ways that consumers of mental health services are active participants in psychiatric treatment. METHODS: Four providers (three psychiatrists and one nurse practitioner) were recruited, and ten consumers with severe mental illness were recruited per provider (40 total). Consumers completed questionnaires on patient activation, illness self-management, and medication attitudes on the day of a psychiatric visit. The visit was audiotaped, transcribed, and thematically analyzed. Providers gave information on diagnosis, substance use disorder, and medication adherence. RESULTS: Consumer-rated patient activation was positively related to illness self-management and negatively related to substance use disorder. Transcripts of the psychiatric visit showed that consumers were active in partnership building, seeking and displaying competence, and directing treatment; however, the relationship was weak between consumer-reported activation and observed activation behaviors. CONCLUSIONS: Consumers were found to be active participants in treatment in a variety of ways, but similar to other populations, the relationship between observed patient activation and consumer-reported desire for involvement was not direct.
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    Coping with Positive and Negative Symptoms of Schizophrenia
    (2010-08) Rollins, Angela L.; Bond, Gary R.; Lysaker, Paul H.; McGrew, John H.; Salyers, Michelle P.
    Objective: Although coping with positive symptoms of schizophrenia has been studied widely, few studies have examined coping with negative symptoms. This study compares the appraisal of stressfulness and coping patterns in response to positive and negative symptoms experienced by clients with schizophrenia attending a community mental health center. Methods: Clients were interviewed to assess symptom severity, appraisal of symptom stressfulness, and coping strategies used for selected symptoms rated as severe and reported as stressful. Open-ended responses from clients regarding coping strategies were coded according to an a priori coding scheme. Results: Clients reported negative symptoms as less stressful, and they used fewer coping strategies in response than they did for positive symptoms. Clients used some types of coping more than others: behavioral more than cognitive, nonsocial more than social, emotion-focused more than problem-focused, and avoidant more than nonavoidant. Conclusions: Clients more often report positive symptoms as stressful compared with negative symptoms, though negative symptoms are still reported as stressful to a certain degree, indicating a need to improve our ability to help clients cope with negative symptoms. Clients are less likely to use coping strategies to counteract negative symptoms compared with positive symptoms. Implications are discussed for developing interventions tailored to promoting awareness of and ways of coping with negative symptoms.
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    Housing Preferences and Choices Among Adults with Mental Illness and Substance Use Disorders: A Qualitative Study
    (2010-08) Tsai, Jack; Bond, Gary R.; Salyers, Michelle P.; Godfrey, Jenna L.; Davis, Kristin E.
    Housing is a crucial issue for adults with severe mental illness and co-occurring substance use disorders, as this population is particularly susceptible to housing instability and homelessness. We interviewed 40 adults with dual disorders, living in either supervised or independent housing arrangements, to examine housing preferences, decision making processes surrounding housing choices, and perceived barriers to housing. We found that many clients indicated their housing preferences had changed over time, and some clients related housing preferences to recovery. Although the majority of clients preferred independent housing, many also described benefits of supervised housing. Clients' current living situations appeared to be driven primarily by treatment provider recommendations and availability of housing. Common barriers to obtaining desired housing were lack of income and information. These findings have implications for supported housing models and approaches to providing housing for clients.
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    Integrating Assertive Community Treatment and Illness Management and Recovery for Consumers with Severe Mental Illness
    (2010-08) Salyers, Michelle P.; McGuire, Alan B.; Rollins, Angela L.; Bond, Gary R.; Mueser, Kim T.; Macy, Veronica R.
    This study examined the integration of two evidence-based practices for adults with severe mental illness: Assertive community treatment (ACT) and illness management and recovery (IMR) with peer specialists as IMR practitioners. Two of four ACT teams were randomly assigned to implement IMR. Over 2 years, the ACT–IMR teams achieved moderate fidelity to the IMR model, but low penetration rates: 47 (25.7%) consumers participated in any IMR sessions and 7 (3.8%) completed the program during the study period. Overall, there were no differences in consumer outcomes at the ACT team level; however, consumers exposed to IMR showed reduced hospital use over time.
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    Staff Turnover in Statewide Implementation of ACT: Relationship with ACT Fidelity and Other Team Characteristics
    (2010-09) Rollins, Angela L.; Salyers, Michelle P.; Tsai, Jack; Lydick, Jennifer M.
    Staff turnover on assertive community treatment (ACT) teams is a poorly understood phenomenon. This study examined annual turnover and fidelity data collected in a statewide implementation of ACT over a 5-year period. Mean annual staff turnover across all observations was 30.0%. Turnover was negatively correlated with overall fidelity at Year 1 and 3. The team approach fidelity item was negatively correlated with staff turnover at Year 3. For 13 teams with 3 years of follow-up data, turnover rates did not change over time. Most ACT staff turnover rates were comparable or better than other turnover rates reported in the mental health and substance abuse literature.