Prescription stimulant use is associated with earlier onset of psychosis.

A childhood history of attention deficit hyperactivity disorder (ADHD) is common in psychotic disorders, yet prescription stimulants may interact adversely with the physiology of these disorders. Specifically, exposure to stimulants leads to long-term increases in dopamine release. We therefore hypothesized that individuals with psychotic disorders previously exposed to prescription stimulants will have an earlier onset of psychosis. Age of onset of psychosis (AOP) was compared in individuals with and without prior exposure to prescription stimulants while controlling for potential confounding factors. In a sample of 205 patients recruited from an inpatient psychiatric unit, 40% (n = 82) reported use of stimulants prior to the onset of psychosis. Most participants were prescribed stimulants during childhood or adolescence for a diagnosis of ADHD. AOP was significantly earlier in those exposed to stimulants (20.5 vs. 24.6 years stimulants vs. no stimulants, p < 0.001). After controlling for gender, IQ, educational attainment, lifetime history of a cannabis use disorder or other drugs of abuse, and family history of a first-degree relative with psychosis, the association between stimulant exposure and earlier AOP remained significant. There was a significant gender × stimulant interaction with a greater reduction in AOP for females, whereas the smaller effect of stimulant use on AOP in males did not reach statistical significance. In conclusion, individuals with psychotic disorders exposed to prescription stimulants had an earlier onset of psychosis, and this relationship did not appear to be mediated by IQ or cannabis.

Early prodromal symptoms can predict future psychosis in familial high-risk youth.

BACKGROUND: Efforts to predict psychosis in individuals at high risk for schizophrenia have focused on the identification of sub-threshold clinical criteria and neurobiological markers, including neuropsychological assessment, structural and functional brain imaging, and psychophysiological testing. We sought to evaluate the relative utility of "psychosis-proneness" measures for prospective prediction of psychotic disorders in a group of young relatives at familial risk for schizophrenia. METHODS: We examined the receiver operating characteristics of sub-threshold symptoms in predicting conversion to psychosis in a group of 97 young first- and second- degree relatives of persons with schizophrenia over a 2-year period. Towards this end, we utilized the Structured Interview of prodromal symptoms to derive measures of two of the four Scale of Prodromal Symptoms subscales (positive and disorganized) and the Chapman Magical Ideation and Perceptual Aberration scales. These four measures were, together, taken to reflect a putative index of psychosis-proneness. RESULTS: Eleven of the 97 subjects developed a psychotic disorder over 2 years of follow-up. Seventeen of the 97 subjects tested positive on this index of psychosis-proneness at baseline and of these 10 converted to psychosis. The sensitivity and specificity of the test were 91 percent and 92 percent respectively. The positive predictive value of the test was 59 percent and its negative predictive value was 99 percent. Addition of measures of cognitive or social function to the index decreased its predictive ability, reducing its specificity and/or sensitivity. CONCLUSIONS: A relatively simple set of clinical measures can be utilized to prospectively identify familial high risk individuals who convert to psychosis with high specificity and sensitivity. Implications for the proposed addition of an "attenuated psychosis syndrome" in DSM-5 are discussed.

Differential processing of metacognitive evaluation and the neural circuitry of the self and others in schizophrenia: a pilot study.

BACKGROUND: Impaired awareness of the self and others (i.e., metacognitive evaluations) are seen in schizophrenia. We compared patterns of activation in schizophrenia (SZ) and nonclinical subjects during a functional magnetic resonance imaging (fMRI) task of metacognitive evaluations that has been demonstrated to engage the neural circuitry of the self in healthy subjects. METHODS: Eleven SZ subjects (7 males, mean age 26.6+/-8) and 10 healthy control subjects (4 males, mean age 29.6+/-8.4) were enrolled. Participants completed two runs of a metacognitive evaluation task (self vs. other vs. word meaning). fMRI data was obtained using a full body Bruker MedSped 4.0Tesla system. Group contrasts were performed using an uncorrected p<0.005 with a 50voxel extent threshold. RESULTS: We observed a significant hypoactivation in the left superior temporal sulcus (STS) during metacognitive evaluations of others (OE) vs. semantic positivity evaluations (SPE) and a trend toward significant hypoactivation in the OE vs. self evaluations (SE) in the SZ group. Significant hypoactivation was also seen in the right inferior temporal gyrus (ITG) in the OE vs. SE contrasts in the SZ group. A trendworthy hypoactivation was seen in the SZ group in the right middle frontal gyrus and pole of the left STS during OE vs. SPE and SE contrasts respectively. CONCLUSIONS: These results extend previous findings of impaired metacognitive evaluative processes in schizophrenia to aberrations of the neural circuitry implicated in self/other awareness among SZ patients. Greater understanding of the neural basis of deficits of self/other awareness in early schizophrenia may contribute to improvements in the identification and treatment of individuals at risk for the illness.

Superior temporal gyrus in schizophrenia: a volumetric magnetic resonance imaging study.

The left superior temporal gyrus (STG) has been reported to be smaller in patients with schizophrenia. The volume of the STG has been found to correlate negatively with severity of hallucinations and thought disorder. In this study, we measured the STG volume of 20 normal controls and 20 patients with schizophrenia using 3 mm contiguous coronal T1 magnetic resonance images. We found that patients had a significantly smaller left anterior STG, and that the volume of this region negatively correlated with the severity of hallucinations. The left posterior STG was not significantly smaller in patients than in controls, but its volume negatively correlated with severity of thought disorder. We also found that the left anterior STG was smaller than the right STG in patients but not in controls. The STG has at least three histologically distinct areas, each with different connections to the rest of the brain. These data are consistent with the proposition that dysfunction of the primary auditory cortex in the anterior and middle STG and auditory association cortex in the posterior STG may play a role in the production of auditory perceptual abnormalities and poor organization of thought respectively.

Acute onset and remission of obsessions and compulsions following medical illnesses and stress.

Obsessive Compulsive Disorder (OCD) is generally chronic. Episodic OCD with complete remission has been rarely reported. Two cases of brief, episodic obsessions and compulsions that appeared for the first time following psychological stress and in the context of medical illness are reported. The possibility of brief episodes of OCD precipitated by stress is illustrated. Exploration of this phenomenon may help us learn more about OCD in general.