Volume Reduction of the Dorsal Lateral Prefrontal Cortex Prior to the Onset of Frank Psychosis in Individuals with an At-Risk Mental State.

Although some individuals with at-risk mental states (ARMS) develop overt psychosis, surrogate markers which can reliably predict a future onset of psychosis are not well established. The dorsal lateral prefrontal cortex (DLPFC) is thought to be involved in psychotic disorders such as schizophrenia. In this study, 73 ARMS patients and 74 healthy controls underwent 1.5-T 3D magnetic resonance imaging scans at three sites. Using labeled cortical distance mapping, cortical thickness, gray matter (GM) volume, and surface area of DLPFC were estimated. These measures were compared across the diagnostic groups. We also evaluated cognitive function among 36 ARMS subjects to clarify the relationships between the DLPFC morphology and cognitive performance. The GM volume of the right DLPFC was significantly reduced in ARMS subjects who later developed frank psychosis (ARMS-P) relative to those who did not (P = 0.042). There was a positive relationship between the right DLPFC volume and the duration prior to the onset of frank psychosis in ARMS-P subjects (r = 0.58, P = 0.018). Our data may suggest that GM reduction of the DLPFC might be a potential marker of future onset of psychosis in individuals with ARMS.

Features of Duration Mismatch Negativity Around the Onset of Overt Psychotic Disorders: A Longitudinal Study.

Reduced amplitude of duration mismatch negativity (dMMN) has been reported in psychotic disorders and at-risk mental state (ARMS); however, few longitudinal MMN studies have examined the amplitude changes during the course of psychosis. We compared dMMN amplitude between ARMS individuals with later psychosis onset and those without, and we longitudinally examined potential dMMN changes around psychosis onset. Thirty-nine ARMS subjects and 22 healthy controls participated in this study. Of the 39 ARMS subjects, 11 transitioned to psychosis (at-risk mental state with later psychosis onset [ARMS-P]) during follow-up and 28 did not (at-risk mental state without later psychosis onset [ARMS-NP]). dMMN was measured twice using an auditory oddball paradigm with a mean interval of 2 years. Follow-up dMMN data were available for all but four ARMS-P subjects. dMMN amplitude at baseline was smaller in ARMS-P subjects compared with control and ARMS-NP subjects. Additionally, ARMS-P subjects displayed a longitudinal decline in dMMN amplitude, which was not present in control and ARMS-P subjects. We also observed a progressive decline in dMMN amplitude during the transition period, suggesting dynamic brain changes associated with the psychosis onset. Our findings implicate dMMN amplitude as a biological predictor of future psychosis onset in high-risk individuals, which may be used for early detection and intervention of psychosis.

Olfactory deficits in individuals at risk for psychosis and patients with schizophrenia: relationship with socio-cognitive functions and symptom severity.

Odor identification deficits are well documented in patients with schizophrenia, but it remains unclear whether individuals at clinical high-risk for psychosis exhibit similar changes and whether their olfactory function is related to social/cognitive functions and symptomatology. In this study, we investigated odor detection sensitivity and identification ability in 32 individuals with at-risk mental state (ARMS), 59 schizophrenia patients, and 169 healthy controls using a T&T olfactometer. The ARMS and schizophrenia subjects were administered the Brief Assessment of Cognition in Schizophrenia (BACS), the Schizophrenia Cognition Rating Scale (SCoRS), and the Social and Occupational Functioning Assessment Scale (SOFAS) to assess their cognitive and social functions, and the Positive and Negative Syndrome Scale (PANSS) for clinical symptoms. Both the ARMS and schizophrenia subjects had lower odor identification ability when compared with healthy controls, while no significant difference was found in the odor detection sensitivity. The lower odor identification ability in the ARMS group correlated with the severity of negative symptoms and weakly correlated with lower performance on the BACS verbal fluency test. The olfactory measures of schizophrenia patients did not correlate with illness duration, medication, symptom severity, and social and cognitive functions. For the ARMS and schizophrenia groups, the olfactory measures did not correlate with the SOFAS and SCoRS scores. These findings suggest that high-risk subjects for psychosis already show odor identification deficits similar to those observed in schizophrenia patients, which probably reflect a biological trait related to vulnerability to psychosis.

Increased Frontal Gyrification Negatively Correlates with Executive Function in Patients with First-Episode Schizophrenia.

Previous neuroimaging studies of gyrification, a possible marker of early neurodevelopment, in schizophrenia patients have reported inconsistent results. In addition, it remains unclear whether aberrant gyrification in schizophrenia patients, if present, is associated with cognitive impairment, which is one of the core features of schizophrenia. Magnetic resonance images were obtained from 62 patients with first-episode schizophrenia and 57 healthy control subjects. Using FreeSurfer software, local gyrification index (LGI) of the entire cortex was compared between the groups. The relationship between LGI and performance in the Wisconsin Card Sorting Test (WCST) was also examined in a subgroup of patients (n= 28). Compared with the controls, the patients showed a significantly higher LGI in a wide range of bilateral frontal regions as well as in the right inferior parietal and bilateral occipital regions. The number of WCST categories archived in patients was negatively correlated with the LGI mainly in the rostral middle frontal and anterior cingulate regions in the right hemisphere. Our findings suggested a widespread hypergyrification pattern in schizophrenia patients, which supported early neurodevelopmental abnormalities. Our results also suggested that executive dysfunction in schizophrenia patients may be at least partly related to aberrant neurodevelopment, especially in the right frontal regions.

Possible relation between olfaction and anxiety in healthy subjects.

AIMS: While olfaction is a sense closely associated with the limbic system and emotions, the relation between emotional status and olfactory functioning has not been well documented. This study aimed to examine the possible effect of anxiety on olfaction in healthy subjects. METHODS: We investigated the effect of state and trait anxiety on the detection and recognition thresholds for five different odors in 124 healthy subjects (62 men and 62 women, mean age = 27.2 years) using a T&T olfactometer. RESULTS: While the influences of age, socioeconomic status, IQ, and smoking history on olfaction were not significant, women had a lower recognition threshold for the odor of sweet fruit and a higher detection threshold for that of rotten food as compared with men. Both state and trait anxiety ratings were significantly associated with reduced olfactory ability, especially for identification of rose odor. CONCLUSIONS: These findings suggest that emotional status affects olfactory functioning in healthy subjects. Our findings may also partly explain the mild olfactory impairment reported in clinical conditions, such as anxiety disorders.

Nomenclature for psychosis risk in Japan: Survey results from high-risk individuals, caregivers, and mental health professionals.

BACKGROUND: Labeling terms for high-risk state for psychosis, such as 'ultra-high risk' (UHR), 'attenuated psychosis syndrome' (APS), and 'at-risk mental state' (ARMS), have been criticized for their potential to lead to stigma. Hence, mental health service users in Melbourne recently proposed new terms illustrating the at-risk concept ['pre-diagnosis stage' (PDS), 'potential of developing a mental illness' (PDMI), and 'disposition for developing a mental illness' (DDMI)]. We aimed at testing the suitability of these existing and new terms in the clinical settings of early psychiatric intervention in Japan. METHODS: At two centers of early intervention (Toyama and Tokyo), a questionnaire on the understanding and opinion of high-risk terminology was administered to 62 high-risk patients, 44 caregivers, and 64 clinicians. The questionnaire contained the existing and new terms, where the term ARMS was translated into two different Japanese terms ARMS-psychosis and ARMS-kokoro. Participants' opinion on the disclosure of high-risk status was also obtained. RESULTS: ARMS-kokoro was most preferred, least stigmatizing, and best explaining the patients' difficulties for all groups, while UHR and other terms including the Japanese word 'psychosis' (i.e., APS and ARMS-psychosis) were not preferred. New labeling terms were generally not well received. All groups preferred full disclosure of high-risk terms by the psychiatrist with or without the presence of family members. CONCLUSION: The term ARMS-kokoro was commonly accepted as a favorable labeling term for the high-risk state for psychosis in Japan. However, another translation ARMS-psychosis was considered stigmatizing, demonstrating the importance of appropriate translation of high-risk terminology into local languages.

Increased pituitary volume in subjects at risk for psychosis and patients with first-episode schizophrenia.

AIM: Enlarged pituitary gland has been reported in schizophrenia, possibly reflecting hypothalamic-pituitary-adrenal hyperactivity. The aim of the present study was to examine whether individuals at risk of psychosis also have similar changes. METHODS: Magnetic resonance imaging was used to examine the pituitary volume in 22 individuals with at-risk mental state (ARMS; 11 male, 11 female), 64 first-episode patients with schizophrenia (FESz; 37 male, 27 female), and 86 healthy controls. The control subjects were divided into age- and gender-matched controls for ARMS (11 male, 11 female) and FESz (37 male, 27 female). RESULTS: Both the ARMS and FESz groups had a larger pituitary volume compared with matched controls, but no difference was found between the ARMS and FESz subjects. There was no association between the pituitary volume and clinical variables (symptommeasures at scanning, daily dosage or duration of antipsychotic medication) in either clinical group. The pituitary volume did not differ significantly between the ARMS individuals who later developed schizophrenia (n = 5) and those who did not (n = 17). The pituitary volume was larger in women than in men for all diagnostic groups. CONCLUSION: The finding of increased pituitary volume in both ARMS and FESz subjects may reflect a common vulnerability to stress in early psychosis. Further work in a larger ARMS sample is required to examine the possible relationship between pituitary volume and emergence of psychosis.

[Early intervention practice in Toyama Prefecture: efforts to improve the clinical service].

We report our activity in the Consultation and Support Service in Toyama (CAST), a clinical service provided by the collaboration of Toyama Prefectural Mental Health Center and University Hospital of Toyama(UHT). About 23% of users diagnosed with at-risk mental state (ARMS), during October 2006 until March 2012, transitioned to overt schizophrenia. More than half of the subjects who continued to visit the specialized clinic in UHT were treated with antipsychotic drugs. We encountered a case of schizophrenia in which early treatment with an atypical psychotic drug was effective in normalizing cognitive function and achieving a good social consequence. The ability of mismatch negativity, an event-related potential, to predict progression to psychosis in subjects with ARMS is discussed. Further efforts should be directed towards improving long-term outcomes, such as social function, for users of the CAST.

Anatomical variations in the insular cortex in individuals at a clinical high-risk state for psychosis and patients with schizophrenia.

Introduction: Since the number of insular gyri is higher in schizophrenia patients, it has potential as a marker of early neurodevelopmental deviations. However, it currently remains unknown whether the features of the insular gross anatomy are similar between schizophrenia patients and individuals at risk of psychosis. Furthermore, the relationship between anatomical variations in the insular cortex and cognitive function has not yet been clarified. Methods: The gross anatomical features (i.e., the number of gyri and development pattern of each gyrus) of the insular cortex were examined using magnetic resonance imaging, and their relationships with clinical characteristics were investigated in 57 subjects with an at-risk mental state (ARMS) and 63 schizophrenia patients in comparison with 61 healthy controls. Results: The number of insular gyri bilaterally in the anterior subdivision was higher in the ARMS and schizophrenia groups than in the control group. The schizophrenia group was also characterized by a higher number of insular gyri in the left posterior subdivision. A well-developed right middle short insular gyrus was associated with symptom severity in first-episode schizophrenia patients, whereas chronic schizophrenia patients with a well-developed left accessory gyrus were characterized by less severe cognitive impairments in motor and executive functions. The features of the insular gross anatomy were not associated with clinical characteristics in the ARMS group. Discussion: The features of the insular gross anatomy that were shared in the ARMS and schizophrenia groups may reflect a vulnerability to psychosis that may be attributed to anomalies in the early stages of neurodevelopment. However, the contribution of the insular gross anatomy to the clinical characteristics of schizophrenia may differ according to illness stages.

Development and validation of a scale of self-alienation-related attributes for the early diagnosis of schizophrenia.

BACKGROUND: The onset of schizophrenia is often preceded by a prodromal phase. However, it is difficult to predict the future transition to schizophrenia from the prodromal symptoms. Based on the diagnostic significance of Schneider's first rank symptoms (FRS), especially those representing "ego disorders (Ichstörungen)", we developed a scale of self-alienation-related attributes (Self-A) to assess the psychological characteristics associated with ego disorders for the early diagnosis of schizophrenia. METHODS: In total, 153 schizophrenia (Sz) patients, 83 at-risk mental state (ARMS) subjects, and 154 healthy control (HC) subjects participated in this study. The Self-A scale was constructed by items from the Minnesota Multiphasic Personality Inventory (MMPI) based on the differences between schizophrenia patients with and without FRS representing ego-disorders designated as "self-alienation symptoms". The Self-A scale was tested for its reliability and validity in a different sample of schizophrenia patients, and was then applied to different cohorts including first-episode schizophrenia (FES) patients, ARMS individuals, and HC subjects. RESULTS: The Self-A consisting of 27 items exhibited good internal consistency reliability. The validity was well demonstrated by the high correlation of the Self-A scores with the self-alienation symptom scores. The ARMS and FES groups had higher Self-A scores than the HC group. The Self-A score in the ARMS individuals who later developed schizophrenia was higher than that in the ARMS subjects who did not, and was comparable with that in the FES group. CONCLUSIONS: This study suggests that the newly developed Self-A scale assessing the self-alienation-related attributes can improve the early diagnosis of schizophrenia.

Thalamic and striato-pallidal volumes in schizophrenia patients and individuals at risk for psychosis: A multi-atlas segmentation study.

Despite previous neuroimaging studies demonstrating morphological abnormalities of the thalamus and other subcortical structures in patients with schizophrenia, the potential role of the thalamus and its subdivisions in the pathophysiology of this illness remains elusive. It is also unclear whether similar changes of these structures occur in individuals at high risk for psychosis. In this study, magnetic resonance imaging was employed with the Multiple Automatically Generated Templates (MAGeT) brain segmentation algorithm to determine volumes of the thalamic subdivisions, the striatum (caudate, putamen, and nucleus accumbens), and the globus pallidus in 62 patients with schizophrenia, 38 individuals with an at-risk mental state (ARMS) [4 of whom (10.5%) subsequently developed schizophrenia], and 61 healthy subjects. Cognitive function of the patients was assessed by using the Brief Assessment of Cognition in Schizophrenia (BACS) and the Schizophrenia Cognition Rating Scale (SCoRS). Thalamic volume (particularly the medial dorsal and ventral lateral nuclei) was smaller in the schizophrenia group than the ARMS and control groups, while there were no differences for the striatum and globus pallidus. In the schizophrenia group, the reduction of thalamic ventral lateral nucleus volume was significantly associated with lower BACS score. The pallidal volume was positively correlated with the dose of antipsychotic treatment in the schizophrenia group. These results suggest that patients with schizophrenia, but not those with ARMS, exhibit volume reduction in specific thalamic subdivisions, which may underlie core clinical features of this illness.

Duration Mismatch Negativity Predicts Remission in First-Episode Schizophrenia Patients.

Objective: Remission in schizophrenia patients is associated with neurocognitive, social, and role functioning during both the early and chronic stages of schizophrenia. It is well-established that the amplitudes of duration mismatch negativity (dMMN) and frequency MMN (fMMN) are reduced in schizophrenia patients. However, the potential link between MMN and remission has not been established. In this study, we investigated the relationship between MMNs and remission in first-episode schizophrenia (FES) and their association with neurocognitive and social functioning. Method: dMMN and fMMN were measured in 30 patients with FES and 22 healthy controls at baseline and after a mean of 3 years. Clinical symptoms and cognitive and social functioning in the patients were assessed at the time of MMN measurements by using the Positive and Negative Syndrome Scale (PANSS), modified Global Assessment of Functioning (mGAF), Schizophrenia Cognition Rating Scale (SCoRS), and the Brief Assessment of Cognition in Schizophrenia (BACS). Remission of the patients was defined using the criteria by the Remission in Schizophrenia Working Group; of the 30 patients with FES, 14 achieved remission and 16 did not. Results: Baseline dMMN amplitude was reduced in FES compared to healthy controls. Further, baseline dMMN in the non-remitters had decreased amplitude and prolonged latency compared to the remitters. MMN did not change during follow-up period regardless of parameters, diagnosis, or remission status. Baseline dMMN amplitude in FES was correlated with future SCoRS and PANSS total scores. Logistic regression analysis revealed that dMMN amplitude at baseline was a significant predictor of remission. Conclusions: Our findings suggest that dMMN amplitude may be a useful biomarker for predicting symptomatic remission and improvement of cognitive and social functions in FES.

Prolonged P300 Latency in Antipsychotic-Free Subjects with At-Risk Mental States Who Later Developed Schizophrenia.

We measured P300, an event-related potential, in subjects with at-risk mental states (ARMS) and aimed to determine whether P300 parameter can predict progression to overt schizophrenia. Thirty-three subjects with ARMS, 39 with schizophrenia, and 28 healthy controls participated in the study. All subjects were antipsychotic-free. Subjects with ARMS were followed-up for more than two years. Cognitive function was measured by the Brief assessment of Cognition in Schizophrenia (BACS) and Schizophrenia Cognition Rating Scale (SCoRS), while the modified Global Assessment of Functioning (mGAF) was used to assess global function. Patients with schizophrenia showed smaller P300 amplitudes and prolonged latency at Pz compared to those of healthy controls and subjects with ARMS. During the follow-up period, eight out of 33 subjects with ARMS developed overt psychosis (ARMS-P) while 25 did not (ARMS-NP). P300 latency of ARMS-P was significantly longer than that of ARMS-NP. At baseline, ARMS-P elicited worse cognitive functions, as measured by the BACS and SCoRS compared to ARMS-NP. We also detected a significant relationship between P300 amplitudes and mGAF scores in ARMS subjects. Our results suggest the usefulness of prolonged P300 latency and cognitive impairment as a predictive marker of later development of schizophrenia in vulnerable individuals.

Reduced Hippocampal Subfield Volume in Schizophrenia and Clinical High-Risk State for Psychosis.

Magnetic resonance imaging (MRI) studies in schizophrenia demonstrated volume reduction in hippocampal subfields divided on the basis of specific cytoarchitecture and function. However, it remains unclear whether this abnormality exists prior to the onset of psychosis and differs across illness stages. MRI (3 T) scans were obtained from 77 patients with schizophrenia, including 24 recent-onset and 40 chronic patients, 51 individuals with an at-risk mental state (ARMS) (of whom 5 subsequently developed psychosis within the follow-up period), and 87 healthy controls. Using FreeSurfer software, hippocampal subfield volumes were measured and compared across the groups. Both schizophrenia and ARMS groups exhibited significantly smaller volumes for the bilateral Cornu Ammonis 1 area, left hippocampal tail, and right molecular layer of the hippocampus than the healthy control group. Within the schizophrenia group, chronic patients exhibited a significantly smaller volume for the left hippocampal tail than recent-onset patients. The left hippocampal tail volume was positively correlated with onset age, and negatively correlated with duration of psychosis and duration of medication in the schizophrenia group. Reduced hippocampal subfield volumes observed in both schizophrenia and ARMS groups may represent a common biotype associated with psychosis vulnerability. Volumetric changes of the left hippocampal tail may also suggest ongoing atrophy after the onset of schizophrenia.

Heschl's Gyrus Duplication Pattern in Individuals at Risk of Developing Psychosis and Patients With Schizophrenia.

An increased prevalence of duplicated Heschl's gyrus (HG), which may reflect an early neurodevelopmental pathology, has been reported in schizophrenia (Sz). However, it currently remains unclear whether individuals at risk of psychosis exhibit similar brain morphological characteristics. This magnetic resonance imaging study investigated the distribution of HG gyrification patterns [i.e., single HG, common stem duplication (CSD), and complete posterior duplication (CPD)] and their relationship with clinical characteristics in 57 individuals with an at-risk mental state (ARMS) [of whom 5 (8.8%) later developed Sz], 63 patients with Sz, and 61 healthy comparisons. The prevalence of duplicated HG patterns (i.e., CSD or CPD) bilaterally was significantly higher in the ARMS and Sz groups than in the controls, whereas no significant differences were observed in HG patterns between these groups. The left CSD pattern, particularly in the Sz group, was associated with a verbal fluency deficit. In the ARMS group, left CSD pattern was related to a more severe general psychopathology. The present results suggest that an altered gyrification pattern on the superior temporal plane reflects vulnerability factors associated with Sz, which may also contribute to the clinical features of high-risk individuals, even without the onset of psychosis.

Potential contribution of pineal atrophy and pineal cysts toward vulnerability and clinical characteristics of psychosis.

BACKGROUND: Magnetic resonance imaging (MRI) studies reported pineal gland atrophy in schizophrenia patients and individuals at a clinical high risk of developing psychosis, implicating abnormalities in melatonin secretion in the pathophysiology of psychosis. However, it currently remains unclear whether the morphology of the pineal gland contributes to symptomatology and sociocognitive functions. METHODS: This MRI study examined pineal gland volumes and the prevalence of pineal cysts as well as their relationship with clinical characteristics in 57 at risk mental state (ARMS) subjects, 63 patients with schizophrenia, and 61 healthy controls. The Social and Occupational Functioning Assessment Scale (SOFAS), the Schizophrenia Cognition Rating Scale (SCoRS), and the Brief Assessment of Cognition in Schizophrenia (BACS) were used to assess sociocognitive functions, while the Positive and Negative Syndrome Scale was employed to evaluate clinical symptoms in ARMS subjects and schizophrenia patients. RESULTS: Pineal gland volumes were significantly smaller in the ARMS and schizophrenia groups than in the controls, while no significant differences were observed in the prevalence of pineal cysts. Although BACS, SCoRS, and SOFAS scores were not associated with pineal morphology, patients with pineal cysts in the schizophrenia group exhibited severe positive psychotic symptoms with rather mild negative symptoms. CONCLUSION: The present results indicate the potential of pineal atrophy as a vulnerability marker in various stages of psychosis and suggest that pineal cysts influence the clinical subtype of schizophrenia.

Reduced cortical thickness of the paracentral lobule in at-risk mental state individuals with poor 1-year functional outcomes.

Although widespread cortical thinning centered on the fronto-temporal regions in schizophrenia has been reported, the findings in at-risk mental state (ARMS) patients have been inconsistent. In addition, it remains unclear whether abnormalities of cortical thickness (CT) in ARMS individuals, if present, are related to their functional decline irrespective of future psychosis onset. In this multicenter study in Japan, T1-weighted magnetic resonance imaging was performed at baseline in 107 individuals with ARMS, who were subdivided into resilient (77, good functional outcome) and non-resilient (13, poor functional outcome) groups based on the change in Global Assessment of Functioning scores during 1-year follow-up, and 104 age- and sex-matched healthy controls recruited at four scanning sites. We measured the CT of the entire cortex and performed group comparisons using FreeSurfer software. The relationship between the CT and cognitive functioning was examined in an ARMS subsample (n = 70). ARMS individuals as a whole relative to healthy controls exhibited a significantly reduced CT, predominantly in the fronto-temporal regions, which was partly associated with cognitive impairments, and an increased CT in the left parietal and right occipital regions. Compared with resilient ARMS individuals, non-resilient ARMS individuals exhibited a significantly reduced CT of the right paracentral lobule. These findings suggest that ARMS individuals partly share CT abnormalities with patients with overt schizophrenia, potentially representing general vulnerability to psychopathology, and also support the role of cortical thinning in the paracentral lobule as a predictive biomarker for short-term functional decline in the ARMS population.

Structural MRI Study of the Planum Temporale in Individuals With an At-Risk Mental State Using Labeled Cortical Distance Mapping.

Background: Recent studies have demonstrated brain structural changes that predate or accompany the onset of frank psychosis, such as schizophrenia, among individuals with an at-risk mental state (ARMS). The planum temporale (PT) is a brain region involved in language processing. In schizophrenia patients, gray matter volume reduction and lack of normal asymmetry (left > right) of PT have repeatedly been reported. Some studies showed progressive gray matter reduction of PT in first-episode schizophrenia patients, and in ARMS subjects during their development of psychosis. Methods: MRI scans (1.5 T field strength) were obtained from 73 ARMS subjects and 74 gender- and age-matched healthy controls at three sites (University of Toyama, Toho University and Tohoku University). Participants with ARMS were clinically monitored for at least 2 years to confirm whether they subsequently developed frank psychosis. Cortical thickness, gray matter volume, and surface area of PT were estimated using FreeSurfer-initiated labeled cortical distance mapping (FSLCDM). PT measures were compared among healthy controls, ARMS subjects who later developed overt psychosis (ARMS-P), and those who did not (ARMS-NP). In each statistical model, age, sex, intracranial volume, and scanning sites were treated as nuisance covariates. Results: Of 73 ARMS subjects, 18 developed overt psychosis (12 schizophrenia and 6 other psychoses) within the follow-up period. There were no significant group differences of PT measures. In addition, significant asymmetries of PT volume and surface area (left > right) were found in all diagnostic groups. PT measures did not correlate with the neurocognitive performance of ARMS subjects. Discussion: Our results suggest that the previously-reported gray matter reduction and lack of normal anatomical asymmetry of PT in schizophrenia patients may not emerge during the prodromal stage of psychosis; taken together with previous longitudinal findings, such PT structural changes may occur just before or during the onset of psychosis.

Association between olfactory sulcus morphology and olfactory functioning in schizophrenia and psychosis high-risk status.

Olfactory impairment has been reported in patients with schizophrenia and individuals with a high risk of psychosis, but its neural basis is largely unknown. We used magnetic resonance imaging to investigate the morphology of the olfactory sulcus (an indicator of olfactory system development) and its relation to olfactory function in 38 persons with an at-risk mental state (ARMS), 62 patients with schizophrenia, and 61 healthy controls. Odor detection and identification were examined with a T & T olfactometer. Compared with the controls, the olfactory sulcus was significantly shallower and odor identification was inferior among the ARMS and schizophrenia subjects. Across all subjects, but not within each group, the olfactory sulcus depth was significantly related to better identification of odors. Our results support the concept that olfactory sulcus morphology reflects the neurodevelopmental process of the olfactory system.

Reduced pineal gland volume across the stages of schizophrenia.

A few magnetic resonance imaging (MRI) studies reported reduced pineal gland volume in chronic schizophrenia (Sz), implicating the involvement of melatonin in the pathophysiology of the illness. However, it is not known whether this abnormality, if present, exists at the early illness stages and/or develops progressively over the course of the illness. This MRI study examined pineal gland volume in 64 patients with first-episode schizophrenia (FESz), 40 patients with chronic Sz, 22 individuals with at-risk mental state (ARMS), and 84 healthy controls. Longitudinal changes in pineal volume (mean inter-scan interval = 2.5 ±â€¯0.7 years) were also examined in a subsample of 23 FESz, 16 chronic Sz, and 21 healthy subjects. In the cross-sectional comparison, the ARMS, FESz, and chronic Sz groups had significantly smaller pineal volume to the same degree as compared with healthy controls. A longitudinal comparison demonstrated that pineal volume did not change over time in any group. There was no association between pineal volume and clinical variables (e.g., symptom severity, medication) in the ARMS and Sz groups. The results suggest that a smaller pineal gland may be a static vulnerability marker of Sz, which probably reflects an early neurodevelopmental abnormality.