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.     

Evidence of gray matter reduction and dysfunction in chromosome 22q11.2 deletion syndrome

Chromosome 22q11.2 deletion syndrome (22q11DS) is associated with cognitive deficits and morphometric brain abnormalities in childhood and a markedly elevated risk of schizophrenia in adolescence/early adulthood. Determining the relationship between neurocognition and neuroimaging findings would yield crucial information about childhood neurodevelopment and provide a basis for the study of the trajectory that occurs on the pathway to psychosis. We compared morphometric brain findings between non-psychotic children with 22q11DS (n = 22) and healthy controls (n = 16), and examined the association between neurocognitive functioning and morphometric brain findings. Volumetric regional gray matter differences between the 22q11DS and control subjects were measured, and correlations of the regional gray matter volumes and neurocognition were performed. Children with 22q11DS demonstrated reductions in gray matter in several brain regions, chiefly the frontal cortices, the cingulate gyrus and the cerebellum. The volumetric reductions in these salient areas were associated with poor performance in sustained attention, executive function and verbal memory; however, the relation of brain volume with cognitive performance did not differ between the patient and control groups. Thus, children with 22q11DS demonstrate gray matter reductions in multiple brain regions that are thought to be relevant to schizophrenia. The correlation of these volumetric reductions with poor neurocognition indicates that these brain regions may mediate higher neurocognitive functions implicated in schizophrenia.     

No difference in the prevalence of cavum septum pellucidum (CSP) between first-episode schizophrenia patients, offspring of schizophrenia patients and healthy controls

The reported prevalence of cavum septum pellucidum (CSP), is extremely variable (from 0.1% to 85%) depending upon the measurement method or imaging resolution. Higher prevalence of CSP has been found in schizophrenia. In this study, we examined the prevalence of CSP in a large number of first-episode schizophrenia patients, young relatives of schizophrenia patients and healthy controls. We manually measured CSP using 1.5 mm T1 MRI scans from ongoing studies at University of Pittsburgh in 89 first-episode patients with schizophrenia (age=23.8+/-7.4, M/F=61/28), 64 genetically at-risk individuals (offspring and siblings of schizophrenia patients, age 15.2+/-3.7, M/F=29/32) and 120 comparison subjects (n=120, age=22.1+/-7.9, M/F62/50). CSP was present in 64% of the first-episode patients (mean length 1.87+/-2.3 mm), 64.6% of the at-risk individuals (1.64+/-1.96 mm) and 64.2% of the normal controls (1.88+/-2.0 mm). There was no difference in the prevalence of CSP exceeding 4 mm. We also did not find any influence of the sex or age in the presence or size of CSP. Our data cast doubt on the significance of CSP as markers of neurodevelopmental pathology in schizophrenia.     

Psychopathology among offspring of parents with schizophrenia: relationship to premorbid impairments

INTRODUCTION: A broad range of psychopathology, including externalizing disorders is seen in offspring at genetic risk for schizophrenia. However, it is unclear whether such psychopathology may underlie a higher predisposition to the premorbid antecedents of schizophrenia. We examined the prevalence and correlates of psychopathology in an ongoing study of offspring genetically at risk for schizophrenia. METHODS: Seventy five consenting high risk offspring (HR: offspring, age 15.68+/-3.27 years; male/female 34/41) and 82 matched comparison subjects (40 males and 42 females; age 15.92+/-3.0 years) participated in this study. Diagnoses were ascertained using structured psychiatric interviews and consensus meetings, including all available clinical information. RESULTS: Sixty (60%) of the HR offspring had one or more lifetime diagnosis of axis I psychiatric disorder. HR subjects with axis I psychopathology had significantly more soft neurological signs, poorer premorbid adjustment, and higher schizotypy scores as measured by Chapman psychosis proneness scales. Among those with psychopathology, HR subjects with externalizing disorders showed the most abnormal scores in schizotypy. DISCUSSION: A substantial proportion of HR offspring of parents with schizophrenia manifest a broad range of childhood psychiatric disorders. Psychopathology, especially externalizing disorders such as attention deficit hyperactivity disorder (ADHD) may represent a subgroup with an increased risk for schizophrenia spectrum disorders. This possibility needs to be examined by prospective follow-up studies, and would be of considerable importance to early diagnosis and intervention efforts in schizophrenia.     

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.     

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

BackgroundEfforts 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.MethodsWe 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.ResultsEleven 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.ConclusionsA 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.     

Do premorbid impairments predict emergent ‘prodromal’ symptoms in young relatives at risk for schizophrenia?

Aims: Individuals at risk for developing schizophrenia (SZ) in the future frequently exhibit subtle behavioural and neurobiological abnormalities in their childhood. A better understanding of the role of these abnormalities in predicting later onset of ‘prodromal’ symptoms or psychosis may help in early identification of SZ. Methods: In an ongoing prospective follow‐up study of young genetically at‐risk relatives of patients with SZ, we studied the prevalence of problems in premorbid social adjustment and childhood psychopathology and examined their relationship with the presence and progression of ‘prodromal’ symptoms of SZ. Results: Growth curve analyses showed that ‘prodromal’ symptoms, as measured by the Scale of ‘Prodromal’ Symptoms, increased during follow‐up. Premorbid maladjustment and childhood behavioural disturbances were cross‐sectionally correlated broadly with ‘prodromal’ symptomatology scores. Longitudinal analyses revealed that behavioural disturbances, but not childhood maladjustment at baseline, significantly predicted increases in ‘prodromal’ symptomatology during the 2‐year study period. Conclusion: Premorbid behavioural disturbance and maladjustment may predict the later emergence of ‘prodromal’ symptoms. ‘Prodromal’ symptoms in young at‐risk relatives may define a subgroup worthy of follow‐up into the age of risk for psychosis in order to cost‐effectively characterize the predictors of psychotic symptoms and SZ.     

Progressive alterations of the auditory association areas in young non-psychotic offspring of schizophrenia patients

Background

Schizophrenia may involve progressive alterations of structure and hemispheric lateralization of auditory association areas (AAA) within the superior temporal gyrus. These alterations may be greater in male patients. It is unclear if these deficits are state-dependent or whether they predate illness onset and reflect familial diathesis.

Aims

We sought to compare AAA cortical thickness, surface area and lateralization across adolescent and young adult non-psychotic offspring of schizophrenia patients (OS) and healthy controls at baseline and one year follow-up. We also assessed the moderating effect of gender on these measures.

Methods

Fifty-six OS and thirty-six control subjects were assessed at baseline and at follow-up on AAA surface area and thickness using FreeSurfer to process T1-MRI-images. We used repeated measures ANCOVAs, controlling intra cranial volume and age with assessment-time and side as within-subject factors and gender and study group as between-subject factors.

Results

Surface area deficit in OS was greater on the left than on the right, as reflected in a lower surface area laterality-index (left-right/left + right  × 100) in OS compared to controls. Left, but not right surface area and surface area laterality-index showed a longitudinal decline in OS compared to controls. Male OS declined more than controls on surface area and thickness.

Conclusions

Left AAA surface area may progressively decline in young non-psychotic offspring at familial diathesis for schizophrenia causing a continuing reversal of the leftward AAA lateralization. Progressive surface area reduction and thinning of AAA may be more prominent in young non-psychotic male offspring at risk for schizophrenia.