Do trauma cue exposure and/or PTSD symptom severity intensify selective approach bias toward cannabis cues in regular cannabis users with trauma histories?

Trauma cue-elicited activation of automatic cannabis-related cognitive biases are theorized to contribute to comorbid posttraumatic stress disorder and cannabis use disorder. This phenomenon can be studied experimentally by combining the trauma cue reactivity paradigm (CRP) with cannabis-related cognitive processing tasks. In this study, we used a computerized cannabis approach-avoidance task (AAT) to assess automatic cannabis (vs. neutral) approach bias following personalized trauma (vs. neutral) CRP exposure. We hypothesized that selective cannabis (vs. neutral) approach biases on the AAT would be larger among participants with higher PTSD symptom severity, particularly following trauma (vs. neutral) cue exposure. We used a within-subjects experimental design with a continuous between-subjects moderator (PTSD symptom severity). Participants were exposed to both a trauma and neutral CRP in random order, completing a cannabis AAT (cannabis vs. neutral stimuli) following each cue exposure. Current cannabis users with histories of psychological trauma (n = 50; 34% male; mean age = 37.8 years) described their most traumatic lifetime event, and a similarly-detailed neutral event, according to an established interview protocol that served as the CRP. As hypothesized, an AAT stimulus type x PTSD symptom severity interaction emerged (p = .042) with approach bias greater to cannabis than neutral stimuli for participants with higher (p = .006), but not lower (p = .36), PTSD symptom severity. Contrasting expectations, the stimulus type x PTSD symptoms effect was not intensified by trauma cue exposure (p = .19). Selective cannabis approach bias may be chronically activated in cannabis users with higher PTSD symptom severity and may serve as an automatic cognitive mechanism to help explain PTSD-CUD co-morbidity.

Glutamate and N-Acetylaspartate Alterations Observed in Early Phase Psychosis: A Systematic Review of Proton Magnetic Resonance Spectroscopy Studies.

Glutamate and N-acetylaspartate have been investigated in the neuropathology of chronic schizophrenia, with fewer studies focusing on early phase psychosis. Additionally, there has been little review and synthesis of the literature focused on multiple brain regions. This systematic review aims to provide a clear report of the current state of research on glutamate and n-acetylaspartate concentrations in early phase psychosis (defined as the first five years following psychosis onset) in multiple brain regions. Existing literature was searched systematically to compile reports of glutamate/glutamate+glutamine (Glx) and n-acetylaspartate absolute levels and ratios in both male and female individuals with early phase psychosis. Reports on glutamate/Glx concentrations in the medial prefrontal region and thalamus were varied, but the majority of reports suggested no alterations in EPP. No studies reported glutamate alterations in the hippocampus or cerebellum. There was no evidence for n-acetylaspartate alterations in the caudate, basal ganglia, and medial prefrontal cortex, and minimal evidence for NAA reductions in the thalamus, anterior cingulate cortex, and hippocampus. Future research should focus on the regions that are less commonly reported, and should aim to explore possible confounds, such as medication status and substance use.

Cannabis and the maturing brain: Role in psychosis development.

A common viewpoint has proliferated that cannabis use is mostly harmless. Some argue that by not supporting its use, we are missing a great therapeutic opportunity. The general public view on cannabis may partially be a result of poor knowledge translation. In fact, the "war on drugs" approach has not allowed for basic education on the varied effects of cannabis on the brain, especially at highly critical phases of brain development such as adolescence.

Toward an integrative understanding of social phobia.

Our objective was to examine the neurobiology of social phobia from the perspectives of basic sciences, genetics, immunology, neuroendocrinology, neurotransmission and neuroimaging and to provide an integrated understanding of social phobia in the framework of a hypothetical neural circuit. Family and twin studies provide evidence that social phobia is heritable with significant genetic influence, and molecular genetics offers possibilities in understanding the nature of the trait that is transmitted. The biologic distinctiveness of social phobia from anxiety disorders and physiological validation of differences between generalized and discrete social phobia subtypes have been implicated in genetic, naturalistic and chemical challenge studies. Evidence of specific dysfunction of dopaminergic, serotonergic, noradrenergic and GABAergic (gamma-aminobutyric acid) neurotransmitter systems has been presented in animal models, challenge studies and treatment investigations. Preliminary neuroimaging research supports previous studies suggesting striatal dopaminergic dysfunction in social phobia and suggests the importance of functional circuits. A neural circuit involving the striatum, thalamus, amygdala and cortical structures may provide a framework for integrating much of the current knowledge on the neurobiology of social phobia.

Global assessment of functioning following assertive community treatment in Edmonton, Alberta: a longitudinal study.

OBJECTIVE: To examine longitudinally the effects of Assertive Community Treatment (ACT) on Global Assessment of Functioning (GAF) scores in Edmonton, Alberta. METHODS: We acquired GAF scores for all clients at initial registration in the ACT program and at subsequent 18- and 36-month time points while in ACT. We analyzed both the entire ACT cohort and separate diagnostic groups. RESULTS: We obtained baseline and follow-up GAF scores for 411 clients, of whom the largest diagnostic group suffered from schizophrenia (n = 189), followed by bipolar disorder (n = 98). Collapsed across all groups, GAF scores significantly improved at both 18 (P < 0.0001) and 36 months (P < 0.0001). By group, at 18-month follow-up, significant improvements were seen in patients with delusional disorder (P < 0.05), dysthymia (P < 0.05), schizoaffective disorder (P < 0.05), and schizophrenia (P < 0.001). This was also seen at 36-month follow-up, with the addition of significant improvements in those with bipolar disorder (P < 0.05). Those patients with major affective disorder or psychosis not otherwise specified (NOS) did not show significant improvements over time. Regardless of diagnosis, those clients with baseline GAF scores of < or = 40 significantly improved at both 18-month (P < 0.0001) and 36-month (P < 0.0001) follow-up, while those with baseline GAF scores above 40 did not show significant improvement. CONCLUSIONS: GAF scores improved at 18- and 36-month follow-up from enrolment in an ACT program. Groups with different diagnoses and levels of functioning at time of enrolment may not benefit to the same degree.

Quetiapine and obsessive-compulsive symptoms (OCS): case report and review of atypical antipsychotic-induced OCS.

The atypical antipsychotics have advanced the treatment of schizophrenia and have proved to be effective agents in treating other disorders with or without psychotic features. We review the literature concerning an increasingly reported and interesting adverse effect, atypical antipsychotic-induced obsessive-compulsive symptoms (OCS). The first known report of quetiapine exacerbating OCS in a 43-year-old man with obsessive-compulsive disorder (OCD), trichotillomania, delusional disorder and bipolar II disorder is presented. Mechanisms, including 5-HT2A and 5-HT2C antagonism, serotonergic regulation of dopamine systems and putative dopaminergic subtypes of OCS and OCD, are discussed. Given the paradoxical efficacy of the atypical antipsychotics in pure OCD, the neurobiology and comorbidity of OCD and schizophrenia, as well as the increasing use of atypical antipsychotics, a cautious and rational pharmacotherapeutic treatment approach is recommended.

Proton magnetic resonance spectroscopy (1H-MRS) of the cerebellum in men with schizophrenia.

OBJECTIVE: To investigate whether there are cerebellar vermis abnormalities in schizophrenia. DESIGN: Prospective imaging study with proton magnetic resonance spectroscopy (1H-MRS). SETTING: Schizophrenia clinic at a large urban hospital. PATIENTS AND CONTROLS: Twelve right-handed male patients with schizophrenia, and 12 control subjects with no psychiatric history. INTERVENTIONS: MRS data were acquired from a 2.0 x 2.0 x 2.0 cm volume of interest that included the entire cerebellar vermis. OUTCOME MEASURES: Spectral peak arising from N-acetylaspartate (NAA), phosphocreatine/creatine (Cr) and choline (Cho). RESULTS: There were no significant differences between the patients with schizophrenia and the controls in cerebellar vermis ratios of NAA to Cr (p = 0.71) or Cho to Cr (p = 0.50). CONCLUSIONS: This study does not support earlier structural studies that found abnormalities of the cerebellar vermis in schizophrenia, although it does support reported neurochemical studies. It does not rule out cerebellar involvement in schizophrenia through mechanisms such as aberrant circuitry. Larger in vivo structural/neurochemical and functional imaging studies in other parts of the cerebellum are needed.

Investigation of Turner syndrome in schizophrenia.

Both Turner syndrome and schizophrenia are relatively infrequent conditions. Consequently, individuals having both illnesses are rare. Previous reviews of sex chromosome abnormalities in schizophrenia have focused primarily on the presence of supernumerary X-chromosomes. After identifying two female patients with schizophrenia and Turner syndrome, we reevaluated the available literature that survey female schizophrenics for the presence of chromosomal abnormalities. Eleven patients with Turner syndrome were identified among 6,483 females with schizophrenia in non-case-report studies. These survey results indicate that Turner syndrome occurs approximately three-fold more frequently in schizophrenic females than in the general female population (P < 0.02). Including 6 other case reports and our 2 cases, a total of 19 females with both schizophrenia and Turner syndrome were reported. Interestingly, whereas most Turner syndrome patients have the 45,X karyotype, the majority (18/19) of women with both illnesses have a mosaic karyotype (P < 0.0002). Given the potential role of genes on the X-chromosome in the pathogenesis of schizophrenia, the study of unique populations with abnormalities in this chromosome, such as women with Turner syndrome, may offer clues into this illness.

Obsessive-compulsive disorder in schizophrenia.

OBJECTIVE: To examine the differences in demographic and clinical features of patients with schizophrenia, with or without comorbid obsessive-compulsive disorder (OCD). METHODS: Fifty-two subjects were recruited from clinical services in the city of Edmonton, Alberta and assessed for schizophrenia and OCD with structured clinical interviews and standardized clinical rating scales. RESULTS: The prevalence of OCD in individuals meeting criteria for schizophrenia was 25%. Those subjects having both schizophrenia and OCD scored significantly higher on the Y-BOCS, Hollingshead scale, and GAF; plus significantly lower PANSS negative symptoms and a trend in increased Parkinsonian symptoms compared with individuals with schizophrenia alone. CONCLUSION: Our preliminary findings indicate that patients with schizophrenia and OCD vary in selected demographic and clinical measures when compared to patients with schizophrenia alone. Patients with schizophrenia and OCD appear to have less negative symptoms, which may thus be reflected in the decreased GAF scores. It is speculated that patients with schizophrenia and OCD may have a greater propensity to basal ganglia dysfunction than those with schizophrenia alone resulting in increased Parkinsonian symptoms.

Drug metabolism and atypical antipsychotics.

The introduction of the atypical antipsychotics clozapine, risperidone, olanzapine, quetiapine and sertindole for the treatment of schizophrenia has coincided with an increased awareness of the potential of drug-drug interactions, particularly involving the cytochrome P450 (CYP) enzymes. The current literature describing the pharmacokinetics of the metabolism of these agents, including their potential to influence the metabolism of other medications, is reviewed. Clozapine appears to be metabolized primarily by CYP1A2 and CYP3A4, with additional contributions by CYP2C19 and CYP2D6. In addition, clozapine may inhibit the activity of CYP2C9 and CYP2C19, and induce CYP1A, CYP2B and CYP3A. Risperidone is metabolized by CYP2D6, and possibly CYP3A4. In vitro data indicate that olanzapine is metabolized by CYP1A2 and CYP2D6. Quetiapine is metabolised by CYP3A4 and sertindole by CYP2D6. There is, however, a general paucity of in vivo data regarding the metabolism of the atypical antipsychotics, indicating a need for further research in this area.

Hospital outcome measures following assertive community treatment in Edmonton, Alberta.

OBJECTIVE: To examine hospital outcome measures for individuals with chronic and severe mental illnesses before and after their registration in an assertive community treatment (ACT) program in Edmonton, Alberta. METHODS: Data were collected from Alberta Health on individuals who were registered in ACT from April 1993 to April 1995. For each individual, hospital outcome measures were calculated for the 365 days prior to and 365 days after registration for ACT (thus covering April 1, 1992-March 31, 1996). RESULTS: Data were collected from 295 individuals. Compared with 1 year prior to beginning ACT, there was a 34% reduction in hospital separations for patients with psychiatric diagnoses. The average length of stay (LOS) for each separated patient decreased by 56%, and the hospitalization days for each patient separated also decreased by 39%. The number of emergency visits for psychiatric reasons was reduced by 32%, and the number of clients visiting emergency departments for psychiatric reasons declined by 30%. CONCLUSIONS: In the 1-year period after registration in an ACT program, hospital outcome measures were improved in this cohort of 295 individuals with severe and chronic mental illnesses.

Obsessive-compulsive disorder in schizophrenia: epidemiologic and biologic overlap.

OBJECTIVE: To examine the co-existence of obsessive-compulsive disorder (OCD) with schizophrenia in terms of epidemiology and overlapping biologic substrates. METHODS: Review of the relevant literature. RESULTS: There appears to be a significant prevalence of OCD in schizophrenia--higher than what would be expected on the basis of calculated comorbidity figures. There is significant overlap in the proposed functional circuits of OCD and schizophrenia, which may lead to co-expression of symptoms. Although there is overlap in neurotransmitter dysfunction, the interactions are complex, especially in regard to the serotonin and dopamine systems. CONCLUSION: The expression of OCD in schizophrenia is complex but very intriguing. Theoretical hypotheses of the pathology of the 2 disorders now need to be tested in larger controlled trials.

Corpus callosum shape and size in male patients with schizophrenia.

BACKGROUND: Corpus callosum (CC) morphology has recently been investigated in schizophrenia using refined imaging and analytic techniques; however, methodological problems and small sample sizes have led to inconsistent findings. METHODS: This study used a large sample of male schizophrenics (n = 79) and male controls (n = 65) to investigate size and shape of the CC on midsagittal magnetic resonance images. Size was determined by tracing the area of the CC, and shape was determined using a landmark-based analysis. In addition, the relationship between CC morphology and phenomenologic variables such as age of onset, length of illness, exposure to medications, and symptom severity was explored. RESULTS: After controlling for age, height, and parental socioeconomic status, there was a main effect of diagnosis on CC size (F = 5.05, df = 1,139, p < .03), with patients' CCs being significantly smaller. No difference was found between patients and controls in CC shape (F = 1.07, df = 18,125, p > .38) or orientation (F = 0.79, df = 18,125, p > .70), using a landmark-based technique. Finally, there was a significant inverse correlation between size of CC and severity of negative symptoms. CONCLUSIONS: These findings support previous studies that have found a decrease in size of the CC in patients with schizophrenia. Moreover, the decrement in volume is generalized, not regional, and is related to the severity of negative symptoms.

A single photon emission computed tomography scan study of striatal dopamine D2 receptor binding with 123I-epidepride in patients with schizophrenia and controls.

The usefulness of 123I-epidepride as a single photon emission computed tomography (SPECT) scan D2 receptor ligand was examined in vivo in 13 medicated patients with schizophrenia and age- and sex-matched normal controls. To establish the effect of endogenous dopamine on 123I-epidepride binding, 4 of the 13 controls also received 20 mg D-amphetamine. The results showed that 123I-epidepride had high specific binding to the striatum in both patients with schizophrenia and normal controls. There was a trend for the total striatal binding of medicated patients with schizophrenia, as measured by total basal ganglia: frontal cortex (TBG:FC) ratios, to be less than the binding of controls (P = 0.053). This trend confirms previous work showing that antipsychotic medication decreases the number of D2 receptors available for binding to the radioligand. Interestingly, there was also a significant relationship between 123I-epidepride binding ratios and global functioning scales (Global Assessment of Functioning scale [GAF]) for schizophrenia (r = 0.56, P = 0.045), although there was no such relationship with the Brief Psychiatric Rating Scale (BPRS). In addition, our results showed that amphetamine-induced dopamine release did not alter 123I-epidepride binding, confirming the high specific binding of 123I-epidepride to the D2 receptor. We conclude that 123I-epidepride appears to be a very useful SPECT ligand for imaging the D2 receptor.