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1.  Impact of Cannabis Use on Long-Term Remission in Bipolar I and Schizoaffective Disorder 
Psychiatry Investigation  2015;12(3):349-355.
To investigate the impact of regular cannabis use on long-term remission of mood symptoms in bipolar spectrum disorders.
The 24-month prospective observational study included patients (n=239) with bipolar I disorder and schizoaffective disorder, bipolar type. Participants were classified as regular cannabis users (three times or more per week) or non-users. The primary outcome measure was the achievement of remission on the evaluations during the 24 months.
Of the 234 participants for whom data was available, 25 (10.7%) were regular cannabis users, and the group comprised significantly more males than females. In the total population, cannabis use was significantly associated with decreased likelihood of remission during the 24-month follow-up period. Subgroup analyses showed that cannabis use was significantly associated with lower remission rates on the Hamilton Depression Rating Scale in females (n=139) and patients prescribed mood stabilizers alone (n=151), whereas in males (n=95) and patients prescribed olanzapine and/or a mood stabilizer (n=83), cannabis use was significantly associated with lower remission rates on the Young Mania Rating Scale. Remission rates were lowest in the concurrent cannabis and tobacco smoking group (n=22) followed by the tobacco smoking only group (n=97), and the non-smoker group (n=116). The post-hoc analysis revealed that all remission rates were significantly lower in the concurrent cannabis and the tobacco smoking group compared to the non-smoker group.
Cannabis use negatively affects the long-term clinical outcome in patients with bipolar spectrum disorders. A comprehensive assessment and integrated management of cannabis use are required to achieve better treatment outcomes for bipolar spectrum disorders.
PMCID: PMC4504917  PMID: 26207128
Cannabis; Bipolar disorder; Schizoaffective disorder; Observational study; Substance; Remission
2.  A Prospective Cohort Study of Antipsychotic Medications in Pregnancy: The First 147 Pregnancies and 100 One Year Old Babies 
PLoS ONE  2014;9(5):e94788.
Many women diagnosed with varying psychiatric disorders take antipsychotic medications during pregnancy. The safety of antipsychotic medications in pregnancy is largely unknown.
We established the National Register of Antipsychotic Medications in Pregnancy in 2005. Women who are pregnant and taking an antipsychotic medication are interviewed every 6 weeks during pregnancy and then followed until their babies are one year old. The baby's progress is closely followed for the first year of life.
As of April 18 2012, 147 pregnancies had been followed through to completion. There were 142 live births and data is available for 100 one year old babies. 18% of babies were born preterm, with a higher dose of antipsychotic medication correlating to an increased likelihood of premature delivery; 43% of babies required special care nursery or intensive care after birth; 37% had any degree of respiratory distress and 15% of babies developed withdrawal symptoms. Congenital anomalies were seen in eight babies. Most pregnancies resulted in the birth of live, healthy babies. The use of mood stabilisers or higher doses of antipsychotics during pregnancy increased the likelihood of babies experiencing respiratory distress or admission to Special Care Nursery or Neonatal Intensive Care Units.
There is a great need for safety and efficacy information about the use of antipsychotic medications in pregnancy. Live, healthy babies are the most common outcome following the use of antipsychotic medication in pregnancy, but clinicians should be particularly mindful of neonatal problems such as respiratory distress.
PMCID: PMC4008497  PMID: 24787688
3.  Primary healthcare practitioners' screening practices and attitudes towards women survivors of child abuse 
Mental Health in Family Medicine  2012;9(3):181-189.
Background Child abuse survivors have an increased risk of developing various mental illnesses in adulthood, which may lead survivors to access primary healthcare services, in particular primary care mental health services.
Aim To determine the frequency with which different primary care mental health practitioners encounter child abuse survivors in their practice and differences in their views about routine screening, level of importance, confidence and comfort in screening and supporting survivors, a cross-sectional study was conducted with 186 practitioners.
Method The sample consisted of general practitioners (13.9%), psychologists (67.9%) and other professions such as psychiatrists, social workers, counsellors, psychotherapists, mental health nurses and other specific mental health practitioners (18.2%).
Results Over 91% of practitioners reported that child abuse was a healthcare issue and was a problem for women in their practice. However, only 51.4% believed that women should be routinely screened for child abuse experiences. Significant differences among practitioner groups were found in aspects of screening and responding to survivors. General practitioners were significantly less likely to screen routinely and reported lower levels of confidence and comfort in conducting screening of survivors when compared with psychologists and other practitioners. The majority of practitioners saw it as psychologists' role to routinely screen; however, 57–82% of practitioners within each group reported that they would benefit from further training in areas relating to asking about and supporting survivors.
Conclusion Findings highlighted further education as a potential area of need to enhance the knowledge and capacity of different practitioner groups in responding to women survivors of child abuse.
PMCID: PMC3622910  PMID: 23997824
child abuse survivors; primary care practitioners; screening
4.  Psychiatrists’ awareness of partial and nonadherence to antipsychotic medication in schizophrenia: results from an Asia–Pacific survey 
Nonadherence is a well-known problem among schizophrenia patients, among whom relapse is fivefold more likely, adversely affecting health, employment, and social functioning. The Spanish Adherencia Terapéutica en la Esquizofrenia (ADHES) survey was developed to determine the scope and causes of medication nonadherence in schizophrenia.
The 20-question ADHES survey was distributed to 19,370 psychiatrists in 13 Asia–Pacific countries in January–April 2012, to ascertain psychiatrists’ perceptions of antipsychotic medication adherence levels among their schizophrenia patients, reasons for partial/nonadherence, their preferred methods of assessing adherence, and strategies to improve adherence. Responses are reported as mean and range across countries.
Four thousand, six hundred sixty one psychiatrists (24% of recipients) completed the survey (highest contributors: People’s Republic of China, 1854; India, 1616). Psychiatrists perceived that 56% (range, 30%–71%) of schizophrenia patients were non- or partially adherent to medication. Patients discontinue medication primarily due to lack of insight into their condition (mean, 37%; 1%–65%) and because patients consider medication unnecessary when feeling better (mean, 27%; 15%–68%). Over half of psychiatrists (mean, 55%; 42%–99%) assess medication adherence at every visit, almost exclusively (81%) by asking their patients, versus quantitative measures. One in three psychiatrists expressed their preference to switch to or add a long-acting antipsychotic to improve adherence (15%–82%).
The substantial prevalence of partial/nonadherence to medication demonstrates that more proactive management of patients with schizophrenia is needed to improve adherence and thereby treatment outcomes.
Registration of this study was not required.
PMCID: PMC3747021  PMID: 23976858
schizophrenia; antipsychotic; APAC; survey; adherence
5.  The Role of Estrogen in the Treatment of Men with Schizophrenia 
Schizophrenia is a debilitating and pervasive mental illness with devastating effects on many aspects of psychological, cognitive and social wellbeing. Epidemiological and life-cycle data point to significant differences in the incidence and course of schizophrenia between men and women, suggesting that estrogen plays a “protective” role . Adjunctive estrogen therapy has been shown to be effective in enhancing the treatment of schizophrenia in women. In men, consideration of estrogen therapy has been impacted by concerns of feminisation, however, clinical trials using estrogen to treat prostate cancer, bone density loss and even aggression in men with dementia or traumatic brain injury, show estrogen to be a safe and effective therapy. Findings do, however, suggest that further exploration of a therapeutic role for adjunctive estradiol treatment in men with schizophrenia is warranted. The development of the new estrogen compounds - Selective Estrogen Receptor Modulators (SERMs) which do not cause feminisation - opens up the possibility of using a different type of estrogen for a longer period of time at higher doses. Estrogen could therefore prove to be an important component in the treatment of psychotic symptoms in men with schizophrenia. This review explains the scientific rationale behind the estrogen hypothesis and how it can be clinically utilised to address concerns unique to the care of men with schizophrenia.
PMCID: PMC3860106  PMID: 24348584
Estrogen; Schizophrenia; Psychosis; Neuroprotection; Men; Selective Estrogen Receptor Modulators
6.  Treatment and outcomes of an Australian cohort of outpatients with bipolar I or schizoaffective disorder over twenty-four months: implications for clinical practice 
BMC Psychiatry  2012;12:228.
The Bipolar Comprehensive Outcomes Study (BCOS) is a 2-year, prospective, non-interventional, observational study designed to explore the clinical and functional outcomes associated with ‘real-world’ treatment of participants with bipolar I or schizoaffective disorder. All participants received treatment as usual. There was no study medication.
Participants prescribed either conventional mood stabilizers (CMS; n = 155) alone, or olanzapine with, or without, CMS (olanzapine ± CMS; n = 84) were assessed every 3 months using several measures, including the Young Mania Rating Scale, 21-item Hamilton Depression Rating Scale, Clinical Global Impressions Scale – Bipolar Version, and the EuroQol Instrument. This paper reports 24-month longitudinal clinical, pharmacological, functional, and socioeconomic data.
On average, participants were 42 (range 18 to 79) years of age, 58%; were female, and 73%; had a diagnosis of bipolar I. Polypharmacy was the usual approach to pharmacological treatment; participants took a median of 5 different psychotropic medications over the course of the study, and spent a median proportion of time of 100%; of the study on mood stabilizers, 90%; on antipsychotics, 9%; on antidepressants, and 5%; on benzodiazepines/hypnotics. By 24 months, the majority of participants had achieved both symptomatic and syndromal remission of both mania and depression. Symptomatic relapse rates were similar for both the CMS alone (65%;) and the olanzapine ± CMS (61%;) cohorts.
Participants with bipolar I or schizoaffective disorder in this study were receiving complex medication treatments that were often discordant with recommendations made in contemporary major treatment guidelines. The majority of study participants demonstrated some clinical and functional improvements, but not all achieved remission of symptoms or syndrome.
PMCID: PMC3570370  PMID: 23244301
7.  Reduced neural activity of the prefrontal cognitive control circuitry during response inhibition to negative words in people with schizophrenia 
Schizophrenia is characterized by deficits in executive control and impairments in emotion processing. This study assessed the nature and extent of potential alterations in the neural substrates supporting the interaction between cognitive control mechanisms and emotion attribution processes in people with schizophrenia.
Functional magnetic resonance imaging was performed during a verbal emotional go/no-go task. People with schizophrenia and healthy controls responded to word stimuli of a prespecified emotional valence (positive, negative or neutral) while inhibiting responses to stimuli of a different valence.
We enrolled 20 people with schizophrenia and 23 controls in the study. Healthy controls activated an extensive dorsal prefrontal–parietal network while inhibiting responses to negative words compared to neutral words, but showed deactivation of the midcingulate cortex while inhibiting responses to positive words compared to neutral words. People with schizophrenia failed to activate this network during response inhibition to negative words, whereas during response inhibition to positive words they did not deactivate the cingulate, but showed increased responsivity in the frontal cortex.
Sample heterogeneity is characteristic of studies of schizophrenia and may have contributed to more variable neural responses in the patient sample despite the care taken to control for potentially confounding variables.
Our results showed that schizophrenia is associated with aberrant modulation of neural responses during the interaction between cognitive control and emotion processing. Failure of the frontal circuitry to regulate goal-directed behaviour based on emotion attributions may contribute to deficits in psychosocial functioning in daily life.
PMCID: PMC3493093  PMID: 22617625
8.  Sensitivity, specificity, and predictive power of the “Brief Risk-resilience Index for SCreening,” a brief pan-diagnostic web screen for emotional health 
Brain and Behavior  2012;2(5):576-589.
Few standardized tools are available for time-efficient screening of emotional health status across diagnostic categories, especially in primary care. We evaluated the 45-question Brief Risk-resilience Index for SCreening (BRISC) and the 15-question mini-BRISC in identifying poor emotional health and coping capacity across a range of diagnostic groups – compared with a detailed clinical assessment – in a large sample of adult outpatients. Participants 18–60 years of age (n = 1079) recruited from 12 medical research and clinical sites completed the computerized assessments. Three index scores were derived from the full BRISC and the mini-BRISC: one for risk (negativity–positivity bias) and two for coping (resilience and social capacity). Summed answers were converted to standardized z-scores. BRISC scores were compared with detailed health assessment and diagnostic interview (for current psychiatric, psychological, and neurological conditions) by clinicians at each site according to diagnostic criteria. Clinicians were blinded to BRISC scores. Clinical assessment stratified participants as having “clinical” (n = 435) or “healthy” (n = 644) diagnostic status. Receiver operating characteristic analyses showed that a z-score threshold of −1.57 on the full BRISC index of emotional health provided an optimal classification of “clinical” versus “healthy” status (sensitivity: 81.2%, specificity: 92.7%, positive predictive power: 80.2%, and negative predictive power: 93.1%). Comparable findings were revealed for the mini-BRISC. Negativity–positivity bias index scores contributed the most to prediction. The negativity–positivity index of emotional health was most sensitive to classifying major depressive disorder (100%), posttraumatic stress disorder (95.8%), and panic disorder (88.7%). The BRISC and mini-BRISC both offer a brief, clinically useful screen to identify individuals at risk of disorders characterized by poor emotion regulation, from those with good emotional health and coping.
PMCID: PMC3489810  PMID: 23139903
Depression and anxiety; emotional well-being; Internet; mental health screen; risk and resilience; sensitivity and specificity
9.  Raloxifene May Have Further Benefits in Women on Hemodialysis 
PMCID: PMC3693644  PMID: 23843841
Raloxifene; Mood; Dialysis
10.  Sequential behavioral treatment of smoking and weight control in bipolar disorder 
People with severe mental illnesses like schizophrenia and bipolar disorder (BPAD) live significantly shorter lives than people in the general population and most commonly die of cardiovascular disease (CVD). CVD risk behaviors such as smoking are not routinely assessed or assertively treated among people with a severe mental illness. This article provides an illustrative case example of a woman with BPAD who is motivated to quit smoking, despite concerns about weight gain and relapse to depression. It outlines key considerations and describes the patient’s experience of participating in a behavioral intervention focussing first on smoking, then diet and physical activity. Clinical challenges encountered during treatment are discussed in the context of relevant literature. These include motivational issues, relapse to depression, medication interactions, weight gain, addressing multiple health behavior change, focussing on a behavioral rather than cognitive approach, collaborating with other health care providers, and gender issues.
PMCID: PMC3717911  PMID: 24073127
Smoking; Smoking cessation; Bipolar disorder; Sequential behavioral treatment; Weight gain; Physical activity
11.  Psychosis and Gender 
PMCID: PMC3420399  PMID: 22966442
12.  Gender Differences in Schizophrenia and First-Episode Psychosis: A Comprehensive Literature Review 
Recent studies have begun to look at gender differences in schizophrenia and first-episode psychosis in an attempt to explain the heterogeneity of the illness. However, a number of uncertainties remain. This paper tries to summarize the most important findings in gender differences in schizophrenia and first-psychosis episodes. Several studies indicate that the incidence of schizophrenia is higher in men. Most of the studies found the age of onset to be earlier in men than in women. Findings on symptoms are less conclusive, with some authors suggesting that men suffer more negative symptoms while women have more affective symptoms. Premorbid functioning and social functioning seem to be better in females than males. However, cognitive functioning remains an issue, with lack of consensus on differences in neuropsychological profile between women and men. Substance abuse is more common in men than women with schizophrenia and first-episode psychosis. In terms of the disease course, women have better remission and lower relapse rates. Lastly, there is no evidence of specific gender differences in familial risk and obstetric complications. Overall, gender differences have been found in a number of variables, and further study in this area could help provide useful information with a view to improving our care of these patients.
PMCID: PMC3420456  PMID: 22966451
13.  The Role of Oestrogen and Other Hormones in the Pathophysiology and Treatment of Schizophrenia 
The theory that many serious mental illnesses, in particular psychoses such as schizophrenia, may have a significant hormonal aetiological component is fast gaining popularity and the support of scientific evidence. Oestrogen in particular has been substantially investigated as a potential mediator of brain function in schizophrenia. Epidemiological and life-cycle data point to significant differences in the incidence and course of schizophrenia between men and women suggests a protective role of oestrogen. In vitro and in vivo preclinical research confirms oestradiol's interactions with central neurotransmitter systems implicated in the pathogenesis of schizophrenia, while results from randomised controlled trials investigating the antipsychotic potential of oestrogen have been positive. Research into other neuroactive hormones with possible effects on mental state is a rapidly evolving field that may hold new promise. Given that schizophrenia and related psychoses are pervasive and debilitating conditions for which currently available treatments are often only partially effective and entail a high risk of serious side-effects, novel therapeutic strategies are needed. The literature reviewed in this paper suggests that hormones such as oestrogen could be a viable option, and it is hoped that with further research and larger trials, the oestrogen hypothesis can be translated into effective clinical practice.
PMCID: PMC3420457  PMID: 22966438

Results 1-13 (13)