Patients with schizophrenia have a high prevalence of cigarette smoking and respond poorly to conventional treatments, highlighting the need for new therapies. We conducted a mechanistic, ...proof-of-concept study using bilateral deep repetitive transcranial magnetic stimulation (dTMS) of insular and prefrontal cortices at high frequency, using the specialized H4 coil. Feasibility of dTMS was tested for disruption of tobacco self-administration, insula target engagement, and insula circuit modulation, all of which were a priori outcomes of interest. Twenty patients completed the study, consisting of weekday dTMS sessions (randomization to active dTMS or sham; double-blind; 10 patients per group), a laboratory tobacco self-administration paradigm (pre/post assessments), and multimodal imaging (three MRI total sessions). Results showed that participants assigned to active dTMS were slower to initiate smoking their first cigarette compared with sham, consistent with smoking disruption. The imaging analyses did not reveal significant Time × Group interactions, but effects were in the anticipated directions. In arterial spin labeling analyses testing for target engagement, an overall decrease in insula blood flow, measured during a post-treatment MRI versus baseline, was numerically more pronounced in the active dTMS group than sham. In fMRI analyses, resting-state connectivity between the insula and default mode network showed a numerically greater change from baseline in the active dTMS group than sham, consistent with a functional change to insula circuits. Exploratory analyses further suggested a therapeutic effect of dTMS on symptoms of psychosis. These initial observations pave the way for future confirmatory studies of dTMS in smoking patients with schizophrenia.
Abstract Background There is evidence of decreased pleasure and deficits in the anticipation of reward in both psychotic illness and drug addiction. Individuals with low anticipatory pleasure may ...preferentially engage in behaviours associated with immediate reward such as cannabis use. Method Ninety-one psychosis patients and 91 controls without history of psychosis were administered the Temporal Experience of Pleasure Scale (TEPS), a self report which measures anticipatory and consummatory pleasure. Cannabis use diagnosis was assessed using the Structured Clinical Interview for DSM IV (SCID). Subjects reported the frequency of cannabis consumption and time since last use. Results Patients did not show a significant deficit in anticipatory or consummatory pleasure compared to controls; however, patients with an active cannabis-use disorder tended to have lower consummatory pleasure than controls with active cannabis disorder (p < .05). Patients who continued to use cannabis during treatment of their first episode of psychosis reported significantly lower anticipatory pleasure compared to those who had a lifetime cannabis diagnosis but were able to maintain abstinence (F(1,60) = 5.6, p = .021). Frequency of cannabis use was negatively correlated to anticipatory and consummatory pleasure (Pearson R = −.46, −.48 respectively) in 37 patients currently using cannabis but not in 46 cannabis-using controls (partial R = −.04, −.07 respectively). Conclusion Anticipatory pleasure may not be decreased in early psychosis patients. Lower hedonic response may be associated with persistent, heavy cannabis use in patients in the early phase of psychotic disorders.
Abstract Deficits in incentive motivation are often present in both Schizophrenia Spectrum Disorders (SSD) and substance-use disorders. The current study aims to test whether the presence of such ...deficits confers vulnerability to cannabis use in individuals with SSD. SSD patients ( n =35) and healthy controls ( n =35) were each divided into a group with ( n =20) and a group without ( n =15) current cannabis use disorder. Subjects performed a behavioural task designed for schizophrenia patients in which they could seek exposure to pleasant and cannabis visual stimuli on the basis of internal representations of these stimuli. Intensity of cannabis use was assessed by self-report. SSD patients were significantly less likely than controls to exert effort to try to re-view pleasant stimuli but were not significantly less likely to work to avoid unpleasant stimuli. Lack of response to re-view pleasant stimuli significantly predicted higher subsequent cannabis self-administration in patients but not controls, after controlling for degree of prior exposure to cannabis. Deficits in incentive motivation may be an aspect of SSD which promotes cannabis use in this population.
This study evaluates how much agreement there is between subjective reports of adherence to antipsychotic medication and objective or derived measures of adherence in first-episode psychosis (FEP) ...and asks if any adherence measure could approximate a gold standard based on correlation to symptom improvement in the early phase of treatment. Adherence was assessed in 81 FEP subjects on a monthly basis by reports from patients, clinicians, family, and pill counting. A consensus measure of adherence was derived from all available sources of adherence data. Symptoms were measured using the Positive and Negative Syndrome Scale at study entry and 3 months subsequently. Adherence as measured by patient report, pill count, and clinician report were in good agreement with each other (intraclass correlation coefficient = 0.84), and all of these measures were highly correlated to consensus adherence (r values between 0.86 and 0.98). Mean adherence was slightly higher as rated by patients (83% full doses taken per month) and family members (91%) than by clinicians (76%), pill counting (73%), or consensus value (74%). Early in treatment, each measure of adherence (except family report) was significantly associated with positive symptom reduction, although the order of magnitude of this correlation was greater for pill count and consensus adherence (P < 0.01) compared with patient- or clinician-reported adherence (P < 0.05). Patient or clinician reports provide a reasonable estimate of medication adherence in FEP, but introducing pill counting or a derived measure of adherence may allow more accurate measurement.
Background Dysfunctional reward processing is present in individuals with schizophrenia-spectrum disorders (SSD) and may confer vulnerability to addiction. Our objective was to identify a deficit in ...patients with SSD on response to rewarding stimuli and determine whether this deficit predicts cannabis use. Methods We divided a group of patients with SSD and nonpsychotic controls into cannabis users and nonusers. Response to emotional and cannabis-associated visual stimuli was assessed using self-report, event-related potentials (using the late positive potential LPP), facial electromyography and skin-conductance response. Results Our sample comprised 35 patients with SSD and 35 nonpsychotic controls. Compared with controls, the patients with SSD showed blunted LPP response to pleasant stimuli ( p = 0.003). Across measures, cannabis-using controls showed greater response to pleasant stimuli than to cannabis stimuli whereas cannabis-using patients showed little bias toward pleasant stimuli. Reduced LPP response to pleasant stimuli was predictive of more frequent subsequent cannabis use (β = −0.24, p = 0.034). Limitations It is not clear if the deficit associated with cannabis use is specific to rewarding stimuli or nonspecific to any kind of emotionally salient stimuli. Conclusion The LPP captures a reward-processing deficit in patients with SSD and shows potential as a biomarker for identifying patients at risk of heavy cannabis use.
Objective:
To determine the validity and reliability of the Alcohol Use Disorders Identification Test (AUDIT) and Drug Abuse Screening Test (DAST) for detecting alcohol and drug use disorders, ...respectively, in a population with first-episode psychosis (FEP).
Method:
Subjects with FEP completed the AUDIT and DAST and were divided into groups according to the presence or absence of a Structured Clinical Interview for DSM-IV (SCID) diagnosis of either current alcohol or drug misuse. The data were analyzed to see whether AUDIT and DAST scores were predictive of SCID diagnosis.
Results:
Patients with alcohol-related SCID diagnoses and those with drug-related SCID diagnoses scored significantly higher on the AUDIT and DAST, respectively, than the group without the respective SCID diagnosis (P < 0.001 in both cases). The AUDIT functioned best with a problem drinking cut-off score of 10 (sensitivity, 85%; specificity, 91%). The DAST functioned best with a problem drug use cut-off score of 3 (sensitivity, 85%; specificity, 73%). The area under the receiver operating characteristic curve was 0.86 for the AUDIT and 0.83 for the DAST.
Conclusion:
The DAST and AUDIT may reliably identify FEP patients with substance abuse.
Abstract Background A history of childhood symptoms of inattention–hyperactivity is often reported in first episode psychosis (FEP) as is cannabis use. In the general population childhood ADHD ...predicts future cannabis use but the relationship has not been tested in FEP. Method Parents of patients with a first episode of psychosis (n = 75) retrospectively assessed their affected child for symptoms of early-life disorders, namely, attention deficit hyperactivity disorder (ADHD), conduct disorder (CD) and oppositional defiant disorder (ODD) using the Child Behaviour Checklist (CBCL). Assessments were made prospectively of cannabis use over two years following a FEP and of SCID diagnosis of cannabis-use disorder. Results Childhood hyperactivity–inattention symptoms predicted inability to maintain abstinence from cannabis following treatment (Wald = 8.4, p = .004) and lifetime cannabis-use diagnosis (Wald = 5.3, p = .022) in a logistic regression controlling for relevant covariates including symptoms of CD and ODD from ages 12 to 18. When the symptom of inattention was considered in place of the hyperactivity–inattention syndrome it predicted cannabis-use diagnosis (Wald = 6.4, p = .011) and persistent abstinence from cannabis (Wald = 5.3, p = .021). Symptoms of CD and ODD did not predict cannabis use when hyperactivity–inattention symptoms were controlled for. Conclusions Symptoms of childhood inattention–hyperactivity predict subsequent cannabis use in FEP.
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