Pan-Canadian study of psychiatric care (PCPC): protocol for a mixed-methods study.

INTRODUCTION: The Canadian population has poor and inequitable access to psychiatric care despite a steady per-capita supply of psychiatrists in most provinces. There is some quantitative evidence that practice style and characteristics vary substantially among psychiatrists. However, how this compares across jurisdictions and implications for workforce planning require further study. A qualitative exploration of psychiatrists' preferences for practice style and the practice choices that result is also lacking. The goal of this study is to inform psychiatrist workforce planning to improve access to psychiatric care by: (1) developing and evaluating comparable indicators of supply of psychiatric care across provinces, (2) analysing variations and changes in the characteristics of the psychiatrist workforce, including demographics and practice style and (3) studying psychiatrist practice choices and intentions, and the factors that lead to these choices. METHODS AND ANALYSIS: A cross-provincial mixed-methods study will be conducted in the Canadian provinces of British Columbia, Manitoba, Ontario and Nova Scotia. We will analyse linked-health administrative data within three of the four provinces to develop comparable indicators of supply and characterise psychiatric services at the regional level within provinces. We will use latent profile analysis to estimate the probability that a psychiatrist is in a particular practice style and map the geographical distribution of psychiatrist practices overlayed with measures of need for psychiatric care. We will also conduct in-depth, semistructured qualitative interviews with psychiatrists in each province to explore their preferences and practice choices and to inform workforce planning. ETHICS AND DISSEMINATION: This study was approved by Ontario Tech University Research Ethics Board (16637 and 16795) and institutions affiliated with the study team. We built a team comprising experienced researchers, psychiatrists, medical educators and policymakers in mental health services and workforce planning to disseminate knowledge that will support effective human resource policies to improve access to psychiatric care in Canada.

Aberrant corticospinal tract characteristics in prodromal PD: A diffusion tensor imaging study.

Introduction: Parkinson's disease (PD) is typically diagnosed when motor symptoms first occur. However, PD-related non-motor symptoms may appear several years before diagnosis. REM sleep behaviour disorder (RBD) and olfactory deficits (hyposmia) are risk factors, but they are not specific for predicting progression towards PD. Other PD-related markers, for example brain imaging markers, may help to identify preclinical PD in hyposmic RBD patients. Studies have reported abnormal structural characteristics in the corticospinal tract (CST) of PD patients, but it is unclear whether hyposmic RBD patients have similar abnormalities that may help to predict PD in these individuals. This study examined whether CST abnormalities may be a potential marker of PD risk by using diffusion tensor imaging (DTI) measures. Methods: Twenty hyposmic RBD patients, 31 PD patients, and 29 healthy controls (HCs) were studied. DTI data were collected on a 1.5 T MRI scanner and CST characteristics (FA, MD, AD, and RD) were evaluated using probabilistic tractography (with seed regions in the bilateral primary motor cortex and mediolateral cerebral peduncles). Olfactory function was assessed with the University of Pennsylvania Smell Identification Test (UPSIT). Results: Hyposmic RBD patients showed significantly higher mean diffusivity (MD) values of the right CST compared to HCs but did not differ from PD patients. PD patients showed a trend of higher MD values compared to HCs. Conclusions: Altered diffusivity in the CST seems to be associated with RBD. The combination of RBD, hyposmia, and CST alterations may be related to later development of PD with comorbid RBD.

Olfactory Function and Diffusion Tensor Imaging as Markers of Mild Cognitive Impairment in Early Stages of Parkinson's Disease.

Parkinson's disease (PD) is a neurodegenerative disorder that is typified by motor signs and symptoms but can also lead to significant cognitive impairment and dementia Parkinson's Disease Dementia (PDD). While dementia is considered a nonmotor feature of PD that typically occurs later, individuals with PD may experience mild cognitive impairment (PD-MCI) earlier in the disease course. Olfactory deficit (OD) is considered another nonmotor symptom of PD and often presents even before the motor signs and diagnosis of PD. We examined potential links among cognitive impairment, olfactory functioning, and white matter integrity of olfactory brain regions in persons with early-stage PD. Cognitive tests were used to establish groups with PD-MCI and with normal cognition (PD-NC). Olfactory functioning was examined using the University of Pennsylvania Smell Identification Test (UPSIT) while the white matter integrity of the anterior olfactory structures (AOS) was examined using magnetic resonance imaging (MRI) diffusion tensor imaging (DTI) analysis. Those with PD-MCI demonstrated poorer olfactory functioning and abnormalities based on all DTI parameters in the AOS, relative to PD-NC individuals. OD and microstructural changes in the AOS of individuals with PD may serve as additional biological markers of PD-MCI.

The impact of depressed mood and coping motives on cannabis use quantity across the menstrual cycle in those with and without pre-menstrual dysphoric disorder.

BACKGROUND AND AIMS: Reported rates of cannabis use among Canadian females are increasing. Female cannabis users progress to cannabis use disorder more rapidly than males (telescoping) and have higher rates of emotional disorder comorbidity. Addictive behaviors may change, along with mood and motivations, across the menstrual cycle (MC), particularly for females with pre-menstrual dysphoric disorder (PMDD). This study aimed to determine whether increases in depressed mood and coping motives would predict increased cannabis use pre-menstrually/menstrually, particularly among females with PMDD. We also assessed positive mood and enhancement motive ratings to establish specificity of predicted depressed mood and coping motive results. DESIGN: Observational study using data collected across 32 days using electronic daily diary methods. SETTING: Nova Scotia, Canada. PARTICIPANTS: Sixty-nine naturally cycling female cannabis users (Mean (M) age = 29.25, Standard Deviation  (SD) = 5.66) with and without retrospectively identified PMDD (via structured clinical interview) and prospectively identified PMDD (via elevated pre-menstrual depressed mood). Self-reported MC phase was validated using salivary progesterone concentrations. MEASUREMENTS: Depressed/positive mood, coping-/enhancement-motivated cannabis use, and cannabis use quantity. FINDINGS: Coping motives explained heightened cannabis use pre-menstrually/menstrually in those with retrospectively identified PMDD. Depressed mood explained increased cannabis use menstrually in those with retrospectively/prospectively identified PMDD. Moreover, prospectively identified PMDD significantly moderated the relationship between depressed mood and cannabis use quantity menstrually. In those with prospectively identified PMDD, positive mood and enhancement motives were associated with decreased cannabis use during the follicular/ovulatory phases. Females with versus without retrospectively identified PMDD also displayed greater overall cannabis use quantity (M [SD] = 3.44[2.84] standard joint equivalents versus 1.85[1.82], respectively; U = 277.50, P = 0.008). CONCLUSIONS: Depressed mood may explain heightened cannabis use menstrually in females with pre-menstrual dysphoric disorder. Coping motives may explain heightened cannabis use pre-menstrually/menstrually in females with retrospectively identified with pre-menstrual dysphoric disorder.

Addictive behaviors across the menstrual cycle: a systematic review.

Research examining relations between menstrual cycle phase and female addictive behaviors is accumulating. Theories suggest addictive behaviors may increase during specific phases of the menstrual cycle resulting from cyclical fluctuations in hormones and affect. In line with self-medication theory, we predicted that addictive behaviors would increase premenstrually and menstrually, phases marked by elevations in negative affect, relative to the follicular and luteal phases. We also hypothesized, coinciding with reward-sensitivity theory, that addictive behaviors may increase during ovulation, a phase characterized by increased positive affect, compared to the same phases. This systematic review summarizes extant literature examining the menstrual cycle phase-addictive behavior relationship and underlying motivations. Articles pertaining to menstrual cycle phase and addictive behaviors within the PsycINFO, CINAL, and PubMED databases were screened to determine eligibility following PRISMA guidelines (n = 1568). Thirty-four articles examining alcohol use, cannabis use, nicotine use, caffeine use, and gambling behavior across menstrual cycle phase met inclusion criteria. Consistent with self-medication theory, strong evidence indicated that nicotine use increased premenstrually and menstrually. Other factors increasing both nicotine and alcohol use premenstrually and menstrually include having a premenstrual dysphoric disorder diagnosis or having premenstrual syndrome. Motivations for using alcohol and nicotine may too vary by menstrual cycle phase. Results were less consistent or understudied for other addictive behaviors and thus conclusions cannot be drawn. Menstrual cycle phase appears to be a female-specific factor affecting some addictive behaviors, particularly nicotine use, and should be considered when conducting addictive behavior research or clinical interventions for reproductive-aged females with addictive disorders.

The impacts of actual and perceived nicotine administration on insula functional connectivity with the anterior cingulate cortex and nucleus accumbens.

BACKGROUND: Changes in resting state functional connectivity between the insula and dorsal anterior cingulate cortex as well as between the insula and nucleus accumbens have been linked to nicotine withdrawal and/or administration. However, because many of nicotine's effects in humans appear to depend, at least in part, on the belief that nicotine has been administered, the relative contribution of nicotine's pharmacological actions to such effects requires clarification. AIMS: The purpose of this study was to examine the impacts of perceived and actual nicotine administration on neural responses. METHODS: Twenty-six smokers were randomly assigned to receive either a nicotine inhaler (4 mg deliverable) or a nicotine-free inhaler across two sessions. Inhaler content instructions (told nicotine vs told nicotine-free) differed across sessions. Resting state functional connectivity between sub-regions of the insula and the dorsal anterior cingulate cortex and nucleus accumbens was measured using magnetic resonance imaging before and after inhaler administration. RESULTS: Both actual and perceived nicotine administration independently altered resting state functional connectivity between the anterior insula and the dorsal anterior cingulate cortex, with actual administration being associated with decreased resting state functional connectivity, and perceived administration with increased resting state functional connectivity. Actual nicotine administration also contralaterally reduced resting state functional connectivity between the anterior insula and nucleus accumbens, while reductions in resting state functional connectivity between the mid-insula and right nucleus accumbens were observed when nicotine was administered unexpectedly. Changes in resting state functional connectivity associated with actual or perceived nicotine administration were unrelated to changes in subjective withdrawal and craving. Changes in withdrawal and craving were however independently associated with resting state functional connectivity between the nucleus accumbens and insula. CONCLUSIONS: Our findings highlight the importance of considering non-pharmacological factors when examining drug mechanisms of action.

Unilateral olfactory sensitivity in multiple sclerosis.

It is not known whether lateralized olfactory sensitivity deficits are present in MS. Since projections from the olfactory bulb to the olfactory cortex are largely ipsilateral, and since both functional imaging and psychophysical studies suggest that the right side of the brain may be more involved in olfactory processing than the left, we addressed this issue by administering well-validated tests of odor detection, along with tests of odor identification, to each side of the nose of 73 MS patients and 73 age-, gender-, and race-matched normal controls. We also determined, in 63 of the MS patients, whether correlations were present between the olfactory test measures and MRI-determined lesions in brain regions ipsilateral and contralateral to the nose side that was tested. No significant left:right differences in either olfactory sensitivity or identification were present, although in both cases mean performance was lower in the MS than in the control subjects (ps<0.0001). Scores on the two sides of the nose were positively correlated with one another (threshold r=0.56, p<0.0001; Identification r=0.71, p<0.0001). The percent of MS patients whose bilateral test scores fell below the 10th percentile of controls did not differ between the odor identification and detection threshold tests. Both left and right odor identification and detection test scores were weakly correlated with lesion volumes in temporal and frontal lobe brain regions (r's<0.40). Our findings demonstrate that MS does not differentially influence odor perception on left and right sides of the nose, regardless of whether sensitivity or identification is being measured. They also indicate that tests of odor identification and detection are similarly influenced by MS and that such influences are associated with central brain lesions.

Olfactory function in psychotic disorders: Insights from neuroimaging studies.

Olfactory deficits on measures of identification, familiarity, and memory are consistently noted in patients with psychotic disorders relative to age-matched controls. Olfactory intensity ratings, however, appear to remain intact while the data on hedonics and detection threshold are inconsistent. Despite the behavioral abnormalities noted, no specific regional brain hypoactivity has been identified in psychosis patients, for any of the olfactory domains. However, an intriguing finding emerged from this review in that the amygdala and pirifom cortices were not noted to be abnormal in hedonic processing (nor was the amygdala identified abnormal in any study) in psychotic disorders. This finding is in contrast to the literature in healthy individuals, in that this brain region is strongly implicated in olfactory processing (particularly for unpleasant odorants). Secondary olfactory cortex (orbitofrontal cortices, thalamus, and insula) was abnormally activated in the studies examined, particularly for hedonic processing. Further research, using consistent methodology, is required for better understanding the neurobiology of olfactory deficits. The authors suggest taking age and sex differences into consideration and further contrasting olfactory subgroups (impaired vs intact) to better our understanding of the heterogeneity of psychotic disorders.

Smoking cue reactivity in current smokers, former smokers and never smokers.

INTRODUCTION: Smoking related stimuli are known to increase both subjective craving and heart rate in smokers; however, little is currently known about the effects of such stimuli in former smokers. METHODS: Subjective craving and heart rate were measured in 38 never smokers, 20 former smokers, and 30 current smokers exposed to video clips containing neutral and smoking related cues. RESULTS: Compared with neutral cues, smoking cues significantly increased both heart rate and self-reported craving in current smokers, while in former smokers smoking cues were associated with a significant decrease in heart rate as well as with a relatively diminished increase in subjective craving. Neither craving nor heart rate was impacted by the smoking cues in never smokers. CONCLUSIONS: Findings suggest that while smoking related stimuli continue to elicit modest subjective cravings in former smokers, there appears to be a marked change in the typical physiological response associated with such stimuli.

The impact of anticipated and unanticipated smoking opportunities on cigarette smoking and nicotine lozenge responses.

BACKGROUND: Perceptions regarding the availability of smoking opportunities are known to affect cigarette craving; however, whether they impact actual smoking or how smokers respond to acute nicotine replacement therapy (NRT) administration is not known. This study examined the impact of pharmacological and expectancy components of NRT administration on craving and smoking in smokers anticipating or not anticipating an imminent smoking opportunity. METHODS: In total, 154 smokers (84 male) completed an experimental session in which instructions regarding the nicotine content of a lozenge (4 mg vs. no nicotine) and regarding the availability of a future smoking opportunity were manipulated. Cigarette craving was assessed before and after manipulations and lozenge administration. All participants were then allotted 1h to self-administer as many cigarette puffs as they wished. RESULTS: Unanticipated smoking opportunities reduced latency to self-administration (p<0.001), regardless of nicotine expectancy or pharmacology. When analyses included all participants, nicotine reduced intentions to smoke (p=0.016) and withdrawal-related craving (p=0.043) regardless of expectancy. Conversely, analyses using only "believers" of the nicotine content instructions revealed that nicotine expectancy reduced intentions to smoke (p=0.034) and withdrawal-related craving (p=0.047) regardless of actual nicotine administration. "Believers" also reported increased withdrawal-related craving when a smoking opportunity was perceived to be imminent (p=0.041). These effects were not significant when analyses included all participants. CONCLUSIONS: Findings suggest that unexpected smoking opportunities may be more appealing than expected ones regardless of perceived or actual acute NRT use. They also highlight the importance of reporting balanced placebo findings using all participants as well as "believers" only.

The impact of nicotine lozenges and stimulus expectancies on cigarette craving.

Reduced craving associated with nicotine replacement therapy use is frequently attributed to the effects of nicotine pharmacology, however non-pharmacological factors may also play a role. This study examined the impact of nicotine pharmacology and non-pharmacological components of an acute nicotine lozenge (4 mg) on cigarette craving, mood and heart rate in 70 daily smokers (36 male). Smoking-related stimuli were used to assess cue-induced craving. Participants were randomly assigned to one of four conditions in a balanced placebo design where half the participants were provided deceptive information regarding the nicotine content of a lozenge. Subjective ratings of craving and mood were collected and heart rate was assessed before and after neutral and smoking cues. Nicotine expectancy reduced withdrawal-related craving (p = 0.006) regardless of actual nicotine administration while combined nicotine expectancy and administration reduced intentions to smoke (p = 0.046) relative to each of the other conditions. Exposure to smoking-related stimuli increased cigarette craving (p ≤ 0.001) and negative affect (p ≤ 0.001) regardless of expectancy or pharmacology. Following the smoking cue, women reported a greater increase in withdrawal-related craving than men (p = 0.027). Findings suggest that both pharmacological and non-pharmacological components of nicotine lozenge administration contribute to its acute effects on craving, yet neither appears effective in preventing craving triggered by exposure to environmental smoking stimuli.

Diffusion tensor imaging and olfactory identification testing in early-stage Parkinson's disease.

Evidence from imaging, clinical studies, and pathology suggests that Parkinson's disease is preceded by a prodromal stage that predates clinical diagnosis by several years but there is no established method for detecting this stage. Olfactory impairment, which is common in Parkinson's disease and often predates clinical diagnosis, may be a useful biomarker for early Parkinson's. Evidence is emerging that diffusion imaging parameters might be altered in olfactory tract and substantia nigra in the early stages of clinical Parkinson's disease, possibly reflecting pathological changes. However, no study has examined olfaction and diffusion imaging in olfactory tract and substantia nigra in the same group of patients. The present study compared newly diagnosed Parkinson's disease patients with a matched control group using both olfactory testing and diffusion tensor imaging of the substantia nigra and anterior olfactory structures. Fourteen patients with stage 1-2 Hoehn & Yahr Parkinson's disease were matched to a control group by age and sex. All subjects then completed the University of Pennsylvania Smell Identification Test, as well as a series of MRI scans designed to examine diffusion characteristics of the olfactory tract and the substantia nigra. Olfactory testing revealed significant impairment in the patient group. Diffusion tensor imaging revealed significant group differences in both the substantia nigra and anterior olfactory region, with fractional anisotropy of the olfactory region clearly distinguishing the Parkinson's subjects from controls. This study suggests that there may be value in combining behavioral (olfaction) and MRI testing to identify early Parkinson's disease. Since loss of olfaction often precedes the motor symptoms in Parkinson's disease, the important question raised is "will the combination of olfactory testing and MRI (DTI) testing identify pre-motor Parkinson's disease?"

An investigation of a possible relationship between olfactory identification deficits at first episode and four-year outcomes in patients with psychosis.

OBJECTIVE: Olfactory identification deficits are found in a significant proportion of patients with schizophrenia spectrum psychotic disorders and appear to be predictive of incomplete remission of negative and cognitive symptoms. In the current study, we examined whether patients with first episode psychosis who have olfactory identification deficits (microsmic) have poorer functional outcome than those whose olfactory status is normal (normosmic). METHOD: Sixty-six (66) first episode psychosis patients (46 M and 20 F) were assessed with the University of Pennsylvania Smell Identification Test (UPSIT) at baseline. UPSIT scores served to classify patients into subgroups. The patients' psychiatrists completed the Social and Occupational Functioning Assessment Scale (SOFAS) and the Levels of Functioning Scale (LOFS) after at least 6 months of treatment. The Premorbid Assessment Scale (PAS) was rated by a parent at baseline. RESULTS: Thirty-eight percent (38%) of the sample was identified as 'microsmic'. LOFS and SOFAS scores were significantly lower in the microsmic group than in the normosmic group. Symptoms were significantly worse in the microsmic group in comparison to the normosmic group. PAS scores did not differ between groups. CONCLUSIONS: First episode patients identified as microsmic at baseline assessment went on to demonstrate poorer functional outcome compared to normosmic patients despite no differences in premorbid adjustment. Olfactory identification deficits at first episode may provide a marker for poorer outcome. Testing olfaction is simple and inexpensive, and could provide clinically valuable information at first episode to identify those patients who might benefit from more intensive interventions promoting functional recovery.

Sex differences in olfactory function in young patients with psychotic disorders.

Female superiority on many measures of olfactory function is well established, but debate remains as to whether this pattern extends to patients with psychotic disorders. The purpose of this large retrospective study was to re-examine whether male vs. female differences in olfactory identification exist in patients with psychotic disorders, and if so, whether any such differences were related to features of the psychotic disorder or could be explained by a generalized male-female difference. We examined 353 relatively young patients, recently diagnosed with a psychotic illness, (258 males and 95 females) and compared these with 89 healthy control subjects (45 males and 44 females). All individuals had been assessed birhinally using the University of Pennsylvania Smell Identification Test (UPSIT). Overall, females were superior to males, and patients underperformed healthy controls. No interaction was noted between these two variables, and there was no significant effect found as a result of age of the subjects. The data suggested that sex differences in olfactory identification ability exist in young patients with psychotic disorders. They do not appear to be related to exposure to antipsychotic medication or smoking habit. Therefore, it is likely that they represent basic male vs. female differences and not diagnosis-specific sex differences in olfactory performance-at least in those who are in the early stages of illness.

Olfactory identification deficits in first-episode psychosis may predict patients at risk for persistent negative and disorganized or cognitive symptoms.

OBJECTIVE: One-third of patients with a schizophrenia spectrum disorder have a measurable olfactory identification deficit at first examination. The authors studied the relationship of this deficit to symptom remission after 1 year of treatment. METHOD: Fifty-eight patients naive to antipsychotic medication who entered the Nova Scotia Early Psychosis Program were symptomatically rated with the Positive and Negative Syndrome Scale (PANSS) (at baseline and 1 year). At baseline, the University of Pennsylvania Smell Identification Test (UPSIT) was also completed. Remission was determined for four symptom factors derived from the PANSS (positive, negative, cognitive/disorganized, and anxiety/depression). Patients with and without remission were compared on UPSIT scores. RESULTS: Patients with nonremission of negative and cognitive/disorganized symptoms had significantly lower baseline UPSIT scores compared with patients with remission. UPSIT scores were unrelated to remission of positive or anxiety/depression symptoms. CONCLUSIONS: UPSIT scores can be used to identify patients at risk for persistent negative and disorganized/cognitive symptoms.

Treatment of a first episode of psychotic illness with quetiapine: an analysis of 2 year outcomes.

BACKGROUND: The first episode of a psychotic disorder provides a unique opportunity to initiate optimal treatment but when a new medication becomes available, little data exist to guide the appropriate use in this population. OBJECTIVES: The objectives were to determine the optimal doses and titration of quetiapine for this group and to measure outcomes (including symptom response, social functioning, mood alterations, motor symptoms, metabolic parameters and cognitive functioning) over 2 years of treatment with quetiapine. DESIGN: Thirty nine subjects with a first episode of psychosis referred to the Nova Scotia Early Psychosis Program in Halifax, Canada, were invited to participate in this study. Standardized clinical, laboratory, and neuropsychological assessments were performed at baseline and following treatment with quetiapine at intervals out to 2 years. RESULTS: Quetiapine was effective in treating the psychotic and mood symptoms while not causing extra-pyramidal signs or symptoms (EPSS). Pre-existing motor dysfunction improved. No anticholinergic medications were required. Several domains of cognitive function also improved (sustained attention, the number of perseverative errors, visuomotor speed and sequencing, verbal fluency and verbal memory). Weight gain was observed along with increases in cholesterol levels but there was no glucose dysregulation. CONCLUSIONS: The results of this two year, naturalistic study of people with a first episode of psychosis indicated that quetiapine was well tolerated and effective for this population. Significant improvements in cognitive functioning also provided evidence for potential longer-term benefits of early and optimal treatment with this agent. However, monitoring metabolic parameters, as recommended for other atypicals, is likely prudent.

The relationship of neuropsychological test performance with the PANSS in antipsychotic naïve, first-episode psychosis patients.

BACKGROUND: Chronic schizophrenia patients have been sampled for factor analytic studies to identify the factor structure of the Positive and Negative Syndrome Scale (PANSS). Many of these studies have identified a cognitive factor, which may provide useful information about patients for whom formal neuropsychological testing is unavailable. However, the relationship between the clinically rated cognitive factor and performance-based cognitive test scores has not been thoroughly examined, particularly in patients who are early in the course of illness. OBJECTIVES: The validity of the PANSS cognitive factor was examined in a sample of antipsychotic naïve, first-episode psychosis patients and the PANSS items that best predicted cognitive functioning were identified. METHOD: PANSS scores and performance on a battery of cognitive tests from the baseline assessment of a clinical trial of 167 neuroleptic naïve patients with schizophrenia-like illnesses were analyzed. RESULTS: Factor analysis revealed a five-factor model that was consistent with previously described factor models from samples of chronically treated patients. There were modest correlations (less than r=0.44) between the derived cognitive factor and six of the neuropsychological test variables (Wisconsin Card Sorting Test total errors and number of categories correctly sorted, WMS-R immediate and delayed recall scores, Category Fluency total score, and WAIS-R digit symbol). Five PANSS items (P6, N5, N6, G2, and G10) were identified that predicted global cognitive functioning; however, 66% of the variance in cognitive functioning remained unexplained. CONCLUSIONS: A PANSS cognitive factor can be identified in first-episode, neuroleptic naïve patients. However, clinical ratings of cognitive deficits lack sensitivity and specificity and thus should not be relied upon fully.