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1.  Couples’ marijuana use is inversely related to their intimate partner violence over the first nine years of marriage 
Research on the association between marijuana use and IPV has generated inconsistent findings, and has been primarily based on cross-sectional data. We examined whether husbands’ and wives’ marijuana use predicted both husbands’ and wives’ IPV perpetration over the first 9 years of marriage (wave 1, n = 634 couples). We also examined moderation by antisocial behavior, the spouse’s marijuana use, and whether IPV was reported during the year prior to marriage. These predictive associations were calculated using a time-lagged multivariate generalized multilevel model, simultaneously estimating predictors of husband and wife IPV. In fully adjusted models, we found that more frequent marijuana use by husbands and wives predicted less frequent IPV perpetration by husbands. Husbands’ marijuana use also predicted less frequent IPV perpetration by wives. Moderation analyses demonstrated that couples in which both spouses used marijuana frequently reported the least frequent IPV perpetration. There was a significant positive association between wives’ marijuana use and wives’ IPV perpetration, but only among wives who had already reported IPV perpetration during the year prior to marriage. These findings suggest there may be an overall inverse association between marijuana use and IPV perpetration in newly married couples, although use may be associated with greater risk of perpetration among women with a history of IPV perpetration.
PMCID: PMC4282761  PMID: 25134048
marijuana; intimate partner violence; marriage; substance use; drug use
2.  Are Statewide Restaurant and Bar Smoking Bans Associated With Reduced Cigarette Smoking Among Those With Mental Illness? 
Nicotine & Tobacco Research  2014;16(6):846-854.
Smoke-free air laws have effectively reduced cigarette consumption at the population level; however, the influence of these policies on smoking among those with mental illness is unclear. We examined whether associations between statewide restaurant/bar smoking bans and cigarette smoking varied by psychiatric diagnoses and gender.
We analyzed data from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC, Wave 1: 2001–2002; Wave 2: 2004–2005; n = 7,317 smokers). All analyses were stratified by gender. We examined whether tobacco cessation was associated with the interaction between ban implementation and Wave 1 psychiatric diagnoses (alcohol use disorder [AUD], anxiety disorder [AD], or mood disorder), adjusting for relevant covariates. Among those who continued to use tobacco at Wave 2, we examined associations between Wave 2 cigarettes per day (CPD) and the diagnoses × ban interactions, controlling for Wave 1 CPD and other relevant covariates.
Among men with an AUD and women with an AD, ban implementation was associated with 6% and 10% greater probability of tobacco cessation at Wave 2, respectively. Among men in the overall sample, ban implementation was associated with smoking 0.8 fewer CPD at Wave 2. Associations with CPD were nonsignificant among women. Interactions between ban implementation and psychiatric diagnoses were also nonsignificant when examining CPD, suggesting consistent reductions in CPD among men but not among women.
This study provided the first evidence that statewide restaurant/bar smoking bans may be associated with reduced smoking among those with select psychiatric conditions.
PMCID: PMC4015101  PMID: 24566280
3.  Consideration of sex in clinical trials of transdermal nicotine patch: A systematic review 
Transdermal nicotine patch (TNP) is one of the most commonly used smoking cessation treatments; however, the efficacy of TNP by sex is not yet clear. The purpose of the current review was to synthesize how sex has been considered in published clinical trials of TNP for smoking cessation. The specific aims of the study were to examine the inclusion of sex in analyses of cessation outcomes, TNP-related variables (compliance, side effects), and quit-related variables (withdrawal, cravings); to review the consideration of sex-related variables (menstrual cycle phase, pregnancy); and to identify needs for future research. Potential articles published through December 31, 2013 were identified through a MEDLINE search of the terms “clinical trial,” “nicotine patch,” and “smoking cessation.” Forty-two studies used all three terms and met the inclusion criteria. Half of the studies reported that they considered sex in smoking cessation outcomes with 14 studies finding no difference by sex and 7 studies finding better outcomes for men versus women. Only 5 studies reported data on outcomes by sex in their publications. No studies reported analysis of TNP compliance or withdrawal by sex. In the one study that examined side effects by sex, more women than men reported discontinuing TNP due to skin irritation. No study examined the association of cessation outcomes with menstrual cycle phase. There is a need to include sex in research on TNP, as well as other pharmacological and behavioral smoking treatments, to clarify the picture of treatment efficacy for women compared to men.
PMCID: PMC4180800  PMID: 25133506
review; smoking; transdermal nicotine patch; sex; clinical trials
4.  Concordant and discordant alcohol, tobacco, and marijuana use as predictors of marital dissolution 
This study examined concordant and discrepant alcohol, tobacco, and marijuana use among couples to determine whether they predicted marital separation/divorce over nine years.
The study recruited 634 couples as they applied for their marriage license and assessed them at that time, and re-assessed them with mailed questionnaires at their 1st, 2nd, 4th, 7th, and 9th anniversaries. Approximately 60% of the men and women were European-American, and approximately 1/3 were African-American. The frequency of drinking to intoxication and binge drinking (more than 5 drinks in an occasion) were assessed, as were the use of cigarettes and marijuana. At each assessment, each member of the couple was asked about the occurrence of marital separations and divorce.
Bivariate analyses indicated that tobacco and marijuana use, whether discrepant or concordant, were associated with marital disruptions. However, discrepant heavy drinking was associated with disruptions but concordant heavy drinking was not. Concordant and discordant marijuana use were not associated with divorce when analyses controlled for alcohol and tobacco use. Concordant and discordant tobacco use was not associated with divorce when analyses controlled for sociodemographic and personality factors. However, discrepant alcohol use was related to divorce after controlling for the other substances in one analysis and after controlling for the sociodemographic factors in a separate analysis.
Tobacco and marijuana use were related to divorce through their associations with other variables. However, results suggested that discrepant alcohol use may lead to marital disruptions and should be addressed with couples seeking marital treatment.
PMCID: PMC4076345  PMID: 24128287
Marriage; Divorce; alcohol use; tobacco; marijuana
5.  Crime and Psychiatric Disorders Among Youth in the US Population: An Analysis of National Comorbidity Survey-Adolescent Supplement 
Current knowledge regarding psychiatric disorders and crime in youth is limited to juvenile justice and community samples. This study examined relationships between psychiatric disorders and self-reported crime involvement in a sample of youth representative of the US population.
The National Comorbidity Survey-Adolescent Supplement (N=10,123; ages 13–17; 2001–2004) was used to examine the relationship between lifetime DSM-IV-based diagnoses, reported crime (property, violent, other), and arrest history. Logistic regression compared the odds of reported crime involvement with specific psychiatric disorders to those without any diagnoses, and examined the odds of crime by psychiatric comorbidity.
Prevalence of crime was 18.4%. Youth with lifetime psychiatric disorders, compared to no disorders, had significantly greater odds of crime, including violent crime. For violent crime resulting in arrest, conduct disorder (CD; OR=57.5; 95% CI=30.4,108.8), alcohol use disorders (OR=19.5; 95% CI=8.8,43.2), and drug use disorders (OR=16.1; 95% CI=9.3,27.7) had the greatest odds with similar findings for violent crime with no arrest. Psychiatric comorbidity increased the odds of crime. Youth with 3 or more diagnoses (16.0% of population) accounted for 54.1% of those reporting arrest for violent crime. Youth with at least 1 diagnosis committed 85.8% of crime, which was reduced to 67.9% by removing those with CD. Importantly, 88.2% of youth with mental illness report never committing any crime.
Our findings highlight the importance of improving access to mental health services for youthful offenders in community settings given the substantial associations found between mental illness and crime in this nationally representative epidemiological sample.
PMCID: PMC4137504  PMID: 25062596
youth; psychiatric disorders; crime; arrest; US population
6.  Super Bowl Sunday: Risky Business for At-Risk (Male) Drinkers? 
Substance use & misuse  2014;49(10):1359-1363.
Major sporting events and other festive occasions are typically associated with alcohol consumption; however, little is known about risky drinking during events such as the “Super Bowl.”
We sought to determine whether drinking on Super Bowl Sunday differed from Saturdays (the heaviest drinking day of the week) surrounding the date of the Super Bowl among at-risk drinkers.
Heavy drinking participants (N = 208) were recruited via advertisements for a two-year prospective study of drinking behaviors. From this larger sample, 196 were selected for whom the date of the Super Bowl was included in their daily alcohol consumption reports (including reports of abstinence on those days) for 2006, 2007, and/or 2008. Participants’ average age was 36.4 (SD = 12.9); 49.5% were women. Participants at the point of recruitment were not seeking treatment and had not been in alcohol treatment in the past year.
Analyses using Multi-Level Modeling comparing Super Bowl Sunday to Saturdays indicated that men drank more alcohol on Super Bowl Sunday across all three years whereas women's drinking was higher in only one of the three years.
These findings suggest that heavy drinking during the Super Bowl (and in association with other sporting events), particularly among men, warrants additional attention due to the potential for deleterious public health consequences.
PMCID: PMC4183053  PMID: 24621086
alcohol consumption; event-specific drinking; celebratory drinking; sporting events; at-risk drinkers
7.  Thalamocortical Projections to Rat Auditory Cortex From the Ventral and Dorsal Divisions of the Medial Geniculate Nucleus 
The ventral and dorsal medial geniculate (MGV and MGD) constitute the major auditory thalamic subdivisions providing thalamocortical inputs to layer IV and lower layer III of auditory cortex. No quantitative evaluation of this projection is available. Using biotinylated dextran amine (BDA)/biocytin injections, we describe the cortical projection patterns of MGV and MGD cells. In primary auditory cortex the bulk of MGV axon terminals are in layer IV/lower layer III with minor projections to supragranular layers and intermediate levels in infragranular layers. MGD axons project to cortical regions designated posterodorsal (PD) and ventral (VA) showing laminar terminal distributions that are quantitatively similar to the MGV-to-primary cortex terminal distribution. At the electron microscopic level MGV and MGD terminals are non-γ-aminobutyric acid (GABA)ergic with MGD terminals in PD and VA slightly but significantly larger than MGV terminals in primary cortex. MGV/MGD terminals synapse primarily onto non-GABAergic spines/dendrites. A small number synapse on GABAergic structures, contacting large dendrites or cell bodies primarily in the major thalamocortical recipient layers. For MGV projections to primary cortex or MGD projections to PD or VA, the non-GABAergic post-synaptic structures at each site were the same size regardless of whether they were in supragranular, granular, or infragranular layers. However, the population of MGD terminal-recipient structures in VA were significantly larger than the MGD terminal-recipient structures in PD or the MGV terminal-recipient structures in primary cortex. Thus, if terminal and postsynaptic structure size indicate strength of excitation then MGD to VA inputs are strongest, MGD to PD intermediate, and MGV to primary cortex the weakest.
PMCID: PMC3320111  PMID: 21618239
electron microscopy; GABA; medial geniculate nucleus
8.  Marijuana withdrawal and aggression among a representative sample of U.S. marijuana users 
Drug and alcohol dependence  2013;132(0):63-68.
Previous laboratory-based research suggests that withdrawal from marijuana may cause increased aggression. It is unclear whether this finding extends beyond the laboratory setting to the general population of marijuana users. The purpose of this study was to test a cross-sectional association between marijuana withdrawal symptoms and aggression among a representative sample of U.S. adult marijuana users, and to test whether this association was moderated by previous history of aggression.
Data were analyzed from the National Epidemiologic Survey on Alcohol and Related Conditions. Wave Two data (2004–2005) were used for all variables except for history of aggression, which was assessed during the Wave One interview (2001–2002). Two outcomes were examined: self-report general aggression and relationship aggression. Odds ratios for aggression based on withdrawal symptoms and the interaction between withdrawal symptoms and history of aggression were calculated using logistic regression, adjusting for covariates and accounting for the complex survey design.
Among marijuana users with a history of aggression, marijuana withdrawal was associated with approximately 60% higher odds of past year relationship aggression (p < 0.05). There was no association between withdrawal symptoms and relationship aggression among those without a history of aggression, and no association with general aggression regardless of history of aggression.
The findings from this study support the notion that laboratory-based increases in aggression due to marijuana withdrawal extend to the general population of marijuana users who have a previous history of aggression.
PMCID: PMC3706470  PMID: 23380439
marijuana; withdrawal; aggression; cannabis; THC; NESARC
9.  Intimate partner violence and specific substance use disorders: Findings from the National Epidemiologic Survey on Alcohol and Related Conditions 
The association between substance use and intimate partner violence (IPV) is robust. It is less clear how the use of specific substances relates to relationship violence. This study examined IPV perpetration and victimization related to the following specific substance use disorders: alcohol, cannabis, cocaine and opioid. The poly-substance use of alcohol and cocaine, as well as alcohol and marijuana were also examined. Data were analyzed from wave two of the National Epidemiologic Study on Alcohol and Related Conditions (2004–2005). Associations between substance use disorders and IPV were tested using logistic regression models while controlling for important covariates and accounting for the complex survey design. Alcohol use disorders and cocaine use disorders were most strongly associated with IPV perpetration, while cannabis use disorders and opioid use disorders were most strongly associated with IPV victimization. A diagnosis of both an alcohol use disorder and cannabis use disorder decreased the likelihood of IPV perpetration compared to each individual substance use disorder. A diagnosis of both an alcohol use disorder and cocaine use disorder increased likelihood of reporting IPV perpetration compared to alcohol use disorders alone, but decreased likelihood of perpetration compared to a cocaine use disorder diagnosis alone. Overall, substance use disorders were consistently related to intimate partner violence after controlling for important covariates. These results provide further evidence for the important link between substance use disorders and IPV, and add to our knowledge of which specific substances may be related to relationship violence.
PMCID: PMC3883081  PMID: 21823768
Intimate partner violence; substance use; mental health; alcohol use; illicit drug use
10.  Spiking in auditory cortex following thalamic stimulation is dominated by cortical network activity 
The state of the sensory cortical network can have a profound impact on neural responses and perception. In rodent auditory cortex, sensory responses are reported to occur in the context of network events, similar to brief UP states, that produce “packets” of spikes and are associated with synchronized synaptic input (Bathellier et al., 2012; Hromadka et al., 2013; Luczak et al., 2013). However, traditional models based on data from visual and somatosensory cortex predict that ascending sensory thalamocortical (TC) pathways sequentially activate cells in layers 4 (L4), L2/3, and L5. The relationship between these two spatio-temporal activity patterns is unclear. Here, we used calcium imaging and electrophysiological recordings in murine auditory TC brain slices to investigate the laminar response pattern to stimulation of TC afferents. We show that although monosynaptically driven spiking in response to TC afferents occurs, the vast majority of spikes fired following TC stimulation occurs during brief UP states and outside the context of the L4>L2/3>L5 activation sequence. Specifically, monosynaptic subthreshold TC responses with similar latencies were observed throughout layers 2–6, presumably via synapses onto dendritic processes located in L3 and L4. However, monosynaptic spiking was rare, and occurred primarily in L4 and L5 non-pyramidal cells. By contrast, during brief, TC-induced UP states, spiking was dense and occurred primarily in pyramidal cells. These network events always involved infragranular layers, whereas involvement of supragranular layers was variable. During UP states, spike latencies were comparable between infragranular and supragranular cells. These data are consistent with a model in which activation of auditory cortex, especially supragranular layers, depends on internally generated network events that represent a non-linear amplification process, are initiated by infragranular cells and tightly regulated by feed-forward inhibitory cells.
PMCID: PMC4168681  PMID: 25285071
auditory cortex; thalamo-cortical (TC); UP states; canonical microcircuit; calcium imaging; multiunit activity; patch clamp
12.  Descending Projections from Extrastriate Visual Cortex Modulate Responses of Cells in Primary Auditory Cortex 
Cerebral Cortex (New York, NY)  2011;21(11):2620-2638.
Primary sensory cortical responses are modulated by the presence or expectation of related sensory information in other modalities, but the sources of multimodal information and the cellular locus of this integration are unclear. We investigated the modulation of neural responses in the murine primary auditory cortical area Au1 by extrastriate visual cortex (V2). Projections from V2 to Au1 terminated in a classical descending/modulatory pattern, with highest density in layers 1, 2, 5, and 6. In brain slices, whole-cell recordings revealed long latency responses to stimulation in V2L that could modulate responses to subsequent white matter (WM) stimuli at latencies of 5–20 ms. Calcium responses imaged in Au1 cell populations showed that preceding WM with V2L stimulation modulated WM responses, with both summation and suppression observed. Modulation of WM responses was most evident for near-threshold WM stimuli. These data indicate that corticocortical projections from V2 contribute to multimodal integration in primary auditory cortex.
PMCID: PMC3183425  PMID: 21471557
calcium imaging; cortical column; layer 5; neocortex; patch clamping
13.  Axonal branching patterns as sources of delay in the mammalian auditory brainstem: a reexamination 
In models of temporal processing, time delays incurred by axonal propagation of action potentials play a prominent role. A preeminent model of temporal processing in audition is the binaural model of Jeffress (1948), which has dominated theories regarding our acute sensitivity to interaural time differences (ITDs). In Jeffress’ model a binaural cell is maximally active when the ITD is compensated by an internal delay, which brings the inputs from left and right ears in coincidence, and which would arise from axonal branching patterns of monaural input fibers. By arranging these patterns in systematic and opposite ways for the ipsi- and contralateral inputs, a range of length differences, and thereby of internal delays, is created so that ITD is transformed into a spatial activation pattern along the binaural nucleus. We reanalyze single, labeled and physiologically characterized, axons of spherical bushy cells of the cat anteroventral cochlear nucleus (AVCN) which project to binaural coincidence detectors in the medial superior olive (MSO). The reconstructions largely confirm the observations of two previous reports, but several features are observed which are inconsistent with Jeffress’ model. We found that ipsilateral projections can also form a caudally-directed delay line pattern, which would counteract delays incurred by caudally-directed contralateral projections. Comparisons of estimated axonal delays with binaural physiological data indicate that the suggestive anatomical patterns cannot account for the frequency-dependent distribution of best delays in the cat. Surprisingly, the tonotopic distribution of the afferents endings indicate that low CFs are under- rather than overrepresented in the MSO.
PMCID: PMC3157295  PMID: 21414923
14.  A unique combination of anatomy and physiology in cells of the rat paralaminar thalamic nuclei adjacent to the medial geniculate body 
The medial geniculate body (MGB) has three major subdivisions - ventral (MGV), dorsal (MGD) and medial (MGM). MGM is linked with paralaminar nuclei that are situated medial and ventral to MGV/MGD. Paralaminar nuclei have unique inputs and outputs when compared with MGV and MGD and have been linked to circuitry underlying some important functional roles. We recorded intracellularly from cells in the paralaminar nuclei in vitro. We found that they possess an unusual combination of anatomical and physiological features when compared to those reported for “standard” thalamic neurons seen in the MGV/MGD and elsewhere in the thalamus. Compared to MGV/MGD neurons, anatomically, 1) paralaminar cell dendrites can be long, branch sparingly and encompass a much larger area. 2) their dendrites may be smooth but can have well defined spines and 3) their axons can have collaterals that branch locally within the same or nearby paralaminar nuclei. When compared to MGV/MGD neurons physiologically 1) their spikes are larger in amplitude and can be shorter in duration and 2) can have dual afterhyperpolarizations with fast and slow components and 3) they can have a reduction or complete absence of the low threshold, voltage-sensitive calcium conductance that reduces or eliminates the voltage-dependent burst response. We also recorded from cells in the parafascicular nucleus, a nucleus of the posterior intralaminar nuclear group, because they have unusual anatomical features that are similar to some of our paralaminar cells. Like the labeled paralaminar cells, parafascicular cells had physiological features distinguishing them from typical thalamic neurons.
PMCID: PMC2943380  PMID: 16566009
calcium burst; intralaminar nuclei; parafascicular nucleus
15.  The Volley theory and the Spherical Cell puzzle 
Neuroscience  2008;154(1):65-76.
Temporal coding in the auditory nerve is strikingly transformed in the cochlear nucleus. In contrast to fibers in the auditory nerve, some neurons in the cochlear nucleus can show “picket fence” phase-locking to low-frequency pure tones: they fire a precisely timed action potential at every cycle of the stimulus. Such synchronization enhancement and entrainment is particularly prominent in neurons with the spherical and globular morphology, described by Osen (1969). These neurons receive large axosomatic terminals from the auditory nerve - the endbulbs and modified endbulbs of Held - and project to binaural comparator nuclei in the superior olivary complex. The most popular model to account for picket fence phase-locking is monaural coincidence detection. This mechanism is plausible for globular neurons, which receive a large number of inputs. We draw attention to the existence of enhanced phase-locking and entrainment in spherical neurons, which receive too few endbulb inputs from the auditory nerve to make a coincidence detection of endbulb firings a plausible mechanism of synchronization enhancement.
PMCID: PMC2486254  PMID: 18424004
temporal coding; binaural; synchronization; amplitude modulation; cochlear nucleus; jitter
16.  Distribution and Kinetic Properties of GABAergic Inputs to Layer V Pyramidal Cells in Rat Auditory Cortex  
Neocortical layer V is distinguished by both its pyramidal cells and its varied cortical and extracortical projections. Several studies suggest that the layer V pyramidal cell types, intrinsically bursting (IB) and regular spiking (RS) cells, differ both in the circuits in which they participate and in their inhibitory inputs. We quantified differences in inhibitory inputs to RS and IB cells using whole-cell voltage clamp techniques in the auditory cortex. We recorded miniature inhibitory postsynaptic currents (mIPSCs) and spontaneous IPSCs to gain kinetic, amplitude, and frequency information about GABAergic synapses. We then used focal sucrose applications to elicit mIPSC rate increases at the soma or dendrites of both cell types. We also electrically stimulated the axons giving rise to inhibitory synaptic inputs to measure minimally evoked IPSCs occurring at the soma or apical dendrites. We found that spontaneous and evoked IPSCs recorded from the auditory cortex have faster rise and decay kinetics when directly compared with those of the same layer V cells in other sensory cortical areas. We also found that mIPSCs observed in auditory IB and RS cells are different from one another. RS cell mIPSCs are larger and have faster rises and decays than IB cell mIPSCs, but IB cell mIPSCs occur more frequently. Focal sucrose application showed that most IB cell mIPSCs originate in the dendrites and are subject to dendritic filtering while most RS cell mIPSCs originate at the soma and are not filtered. These findings suggest that, first, IB and RS cells process their inputs in fundamentally different ways and, second, auditory cortical RS and IB cells may have specializations that allow them to process inhibitory inputs faster.
PMCID: PMC3202454  PMID: 12209293
18.  Address in Medicine 
British Medical Journal  1900;2(2066):280-284.
PMCID: PMC2463287  PMID: 20759136

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