الفهرس 
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Abstract
Bipolar disorder remains a prevalent and serious psychiatric disorder. Although a number of pharmacological treatments for bipolar disorder exist, including mood stabilizers such as lithium and valproic acid, none have emerged as singularly effective against all aspects of the illness. Furthermore, the large range of available remedies implies a poor understanding of the underlying pathophysiology of bipolar disorder.
Magnetic resonance spectroscopy (MRS) affords a noninvasive window on in vivo brain chemistry and, as such, provides a unique opportunity to gain insight into the biochemical pathology of bipolar disorder. Studies utilizing proton (1H) MRS have identified changes in cerebral concentrations of N-acetyl aspartate (NAA), choline (Cho)-containing compounds, and creatine (cr) in bipolar subjects compared to normal controls and to schizophrenia.
Bipolar disorder and schizophrenia also demonstrate some similarities in neurotransmitter dysfunction. As further indirect evidence of a possible association, many newer atypical antipsychotic agents approved for the treatment of schizophrenia are also proving useful for bipolar disorder.
OBJECTIVES
The purpose of this study was to Identify neurochemical alterations in patients with bipolar disorder; the concentration of NAA, Cho and Cr containing compounds in frontal lobes, hippocampi, and thalami of patients which may enhance our understanding of the neurophysiology. Another aim was to compare ratios of metabolites in patients with bipolar disorder and healthy subjects, to compare ratios of our findings regarding metabolites in patients with bipolar disorder and findings of other studies in patients with schizophrenia. Finally the relationship between ratios of metabolite and clinical variables was examined in the study.
METHODS
1H MRS was performed in 25 patients with bipolar disorder and 20 ages matched healthy subjects in the three cerebral areas highly involved in pathophysiology of Bipolar (frontal lobes, hippocampi, and thalami) the Comparable values of for NAA, Cr, and Cho have been taken. Modified mania rating scale was applied to patient with manic episode while H-DRS was applied to patient with depression episode in addition to SCID-I
RESULTS
The results of the study were that substantial evidence that the distribution of the metabolite alterations in the brain is significantly different in the 3 groups. Comparing patients with bipolar disorder with the group of the control, there were significant differences have been found in the ratios in both thalami and both frontal lobes; NAA/Cr in the right thalamus (U=140, Z= -2.514, P = 0.012), NAA/Cr in the left thalamus (U=131, Z=-2.244, p=0.025), NAA/Cr in the right frontal (U=131, Z=-2.244, p=0.025), and Cho/Cr left frontal (U=134.5, Z=-2.328, p=0.020). By comparing the patients with bipolar to the patients with schizophrenia there were significant higher NAA/Cr in patients with bipolar than in patients with schizophrenia in both thalami, both hippocampi and right frontal; NAA/Cr in the right thalamus (U=155.5, Z=-3.047, p=0.002), NAA/Cr in the left thalamus (U=107, Z=3.989, p=0.000), NAA/Cr in the right frontal (U=116, Z=-3.392, p=0.001), NAA/Cr in the right hippocampus (U=168.5, Z=-2.458, p=0.014), and NAA/Cr in the left hippocampus(U=63.5, Z=-4.265, p=0.000). No significant between the metabolites and presence of psychotic symptoms, gender, family history of affective disorder, and duration of the entire disorder. Cho/Cr ratio was significantly lower in the left frontal lobes in patients with more than one episode compared to patients presented with single episode (t=2.558, p=o.019). Significantnegative correlations were found between age and NAA/Cho in the right thalamus, NAA/Cr in the right frontal, and NAA/Cho in the left frontal. Significant negative correlation has been found between age at onset and NAA/Cho in the left frontal., There was a significant negative correlation has been found between severity of depression and Cho/Cr in the left hippocampus and significant negative correlations have been found between severity of mania and NAA/Cr in the left frontal. There were significant lower metabolite ratios in patient with bipolar, depression episode when compared to patients with bipolar, manic episode; NAA/Cr in the right thalamus (t=-2.415, p=0.024), NAA/Cho in the right frontal (t=-4.517, p=0.000), NAA/Cho in the left frontal (t=-2.526, p=0.019), NAA/Cr in the left frontal (t=-4.627, p=0.000).
CONCLUSIONS
The principal conclusion that there were significant differences have been found in the ratios in both thalami and both frontal lobes between patients with bipolar disorder and the group of the control; higher NAA/Cr in both thalami and right frontal lobe and lower Cho/Cr in left frontal in bipolar than the control.
The high NAA/Cr could be consistent with neurobiological models of BPD postulating increased activity in the cortexand/or neurodevelopmental theories BPDaccording to which such disorder would result from abnormal neuronal pruning.
There was higher NAA/Cr in the right frontal in patients with bipolar than in the control, and lower Cho/Cr in left frontal in bipolar than the control which supports the view that limbic hyperactivity and frontal hypoactivity are neurobiological correlates of bipolar disorder.
Moreover it supports that the thalamus is a key structure within the circuits that modulate mood states and might thus play an important role within the etiology of the bipolar affective disorder.
The other important findings were that, therewere significant higher NAA/Cr in patients with bipolar than in patients with schizophrenia in both thalami, both hippocampi and right frontal.
These findings are suggestive of a long-term failure of energy production in the brain in schizophrenia. This interpretation is consistent with previous findings of mitochondrial dysfunction in schizophrenia.
Brain metabolites are not affected by psychotic symptoms, gender, family history of affective disorder, nor duration of the entire disorder while they’re affected by number of episodes, age, age at onset, and severity of the current episode.